Publications (5)20.83 Total impact
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Article: Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy.
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ABSTRACT: The clinical course of patients with dilated cardiomyopathy (DCM) varies from cardiac recovery to end stage heart failure. The etiology of this variability is largely unknown. In this study, we investigated the impact of coding polymorphisms of the innate immune protein Toll-like receptor 4 (TLR4) on left ventricular performance in patients with DCM. Two variants of TLR4 (rs4986790, TLR4 c.1187A→G, p.299D→G and rs4986791,TLR4 c.1487C→T, p.T399I) were investigated in 158 patients with DCM. Other reasons for heart failure were excluded by coronary angiography, myocardial biopsy, and echocardiography. Risk factors, age, gender, or treatment did not differ among the groups. At the follow-up evaluation (median 4.0-5.4 months), patients carrying the TLR4 wild type gene displayed cardiac recovery under intense medical heart failure therapy indexed by reduced left ventricular dilation, improved left ventricular ejection fraction, and reduced NT-probrain natriuretic peptide blood level when compared with the initial evaluation. In contrast, patients carrying both the rs4986790 and the rs4986791 variant showed significantly reduced improvement of left ventricular ejection fraction (p = 0.006) and left ventricular dilation (p = 0.015) at the follow-up evaluation when compared with carriers of the wild type gene under the same treatment conditions. In addition, NT-probrain natriuretic peptide level in carriers of both TLR4 variants did not change significantly at the follow up when compared with the first evaluation. Among patients with DCM, the presence of the TLR4 variants rs4986790 and rs4986791 predicts impaired cardiac recovery independently of medical treatment or cardiac risk factors.Journal of Biological Chemistry 05/2012; 287(32):27236-43. · 4.77 Impact Factor -
Article: Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies.
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ABSTRACT: Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Continuous ABI and PAD (ABI ≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fixed effects inverse variance weighted meta-analyses. There were a total of 41 692 participants of European ancestry (≈60% women, mean ABI 1.02 to 1.19), including 3409 participants with PAD and with genome-wide association study data available. In the discovery meta-analysis, rs10757269 on chromosome 9 near CDKN2B had the strongest association with ABI (β=-0.006, P=2.46×10(-8)). We sought replication of the 6 strongest SNP associations in 5 population-based studies and 3 clinical samples (n=16 717). The association for rs10757269 strengthened in the combined discovery and replication analysis (P=2.65×10(-9)). No other SNP associations for ABI or PAD achieved genome-wide significance. However, 2 previously reported candidate genes for PAD and 1 SNP associated with coronary artery disease were associated with ABI: DAB21P (rs13290547, P=3.6×10(-5)), CYBA (rs3794624, P=6.3×10(-5)), and rs1122608 (LDLR, P=0.0026). Genome-wide association studies in more than 40 000 individuals identified 1 genome wide significant association on chromosome 9p21 with ABI. Two candidate genes for PAD and 1 SNP for coronary artery disease are associated with ABI.Circulation Cardiovascular Genetics 12/2011; 5(1):100-12. · 6.11 Impact Factor -
Article: Effects of immunoadsorption and subsequent immunoglobulin G substitution on cardiopulmonary exercise capacity in patients with dilated cardiomyopathy.
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ABSTRACT: Recent data indicate that cardiac antibodies play an active role in the pathogenesis of dilated cardiomyopathy (DCM) and may contribute to cardiac dysfunction in patients with DCM. The present study investigated the influence of immunoadsorption with subsequent immunoglobulin G substitution (IA/IgG) on cardiopulmonary exercise capacity in patients with DCM. Sixty patients with DCM (New York Heart Association II-IV, left ventricular ejection fraction < or =45%) were included in this single-center university hospital-based case-control study. Patients either were treated with IA/IgG (n = 30) or were followed without IA/IgG (n = 30). At baseline and after 3 months, we compared echocardiographic assessment of left ventricular function and spiroergometric exercise parameters. In contrast to controls, left ventricular ejection fraction improved significantly in the IA/IgG group from 33.0% +/- 1.2% to 40.1% +/- 1.5% (P < .001). In the control group, spiroergometric exercise parameters did not change during follow-up. After 3 months, maximum achieved power increased in the treatment group from 114.2 +/- 7.4 to 141.9 +/- 7.9 W (P = .02). Total exercise time increased in the treatment group from 812 +/- 29 to 919 +/- 30 seconds (P < .05). Peak oxygen uptake (Vo(2)) increased from 17.3 +/- 0.9 to 21.8 +/- 1.0 mL min(-1) kg(-1) after IA/IgG (P < .01). Oxygen pulse (peak Vo(2)/maximum heart rate) increased in the treatment group (10.7 +/- 0.7 vs 13.6 +/- 0.7 mL beat(-1) min(-1), P < .01). The Vo(2) at the gas exchange anaerobic threshold increased after 3 months in the treatment group from 10.3 +/- 0.5 to 13.2 +/- 0.5 mL min(-1) kg(-1) (P < .001). The ventilatory response to exercise (V(E)/Vco(2) slope) decreased after IA/IgG therapy from 32.3 +/- 1.5 to 28.7 +/- 0.9 (P = .02). In patients with DCM, IA/IgG therapy may induce improvement in echocardiographic and cardiopulmonary exercise parameters.American heart journal 05/2010; 159(5):809-16. · 4.65 Impact Factor -
Article: The cardiovascular safety of tadalafil.
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ABSTRACT: Tadalafil is an inhibitor of phosphodiesterase 5, approved for the treatment of erectile dysfunction. Blood pressure-lowering effects of tadalafil in healthy volunteers are minimal. In patients on a broad spectrum of antihypertensive medication, severe hypotension did not occur in combination with tadalafil; however, a combination of tadalafil with any nitric oxide donor can lead to life-threatening hypotension and is, therefore, absolutely contraindicated (at least 48 h interval after last dose of tadalafil). Combination with alpha-blocking agents, such as doxazosin, may only be considered when patients are hemodynamically stable for a longer period using the lowest dose of tadalafil and with close blood pressure monitoring. In placebo-controlled trials, severe adverse cardiovascular events were rare in tadalafil users and similar in frequency in comparison to placebo. However, as cardiovascular disease is highly prevalent in patients with erectile dysfunction, a complete diagnostic work up of these patients and potentially optimized cardiovascular treatment may be necessary before sexual intercourse can be recommended and tadalafil may be prescribed.Expert Opinion on Drug Safety 02/2008; 7(1):43-52. · 3.02 Impact Factor -
Article: Acute Hemodynamic Effects of [beta]-Blockers in Patients with Severe Congestive Heart Failure: Comparison of Celiprolol and Esmolol
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ABSTRACT: The present study was designed to investigate, in patients with severe heart failure, the dose-dependent acute hemodynamic effects of celiprolol versus those of esmolol. Celiprolol is a β 1 -receptor blocker with vasodilating properties, whereas esmolol is an ultra-short-acting β 1 -blocker. Included were 14 patients with decompensated chronic heart failure (NYHA class IV) due to coronary heart disease (n = 8) or to dilated cardiomyopathy (n = 6). Each patient received both celiprolol and esmolol in random fashion. The β-blockers were administered in four dose tiers, with an increase in dosage every 15 min. Hemodynamic measurements were obtained with a Swan-Ganz thermodilution catheter. Administration of celiprolol (5, 10, 20, and 50 μg/kg) took place intravenously. After intravenous administration of a loading dose of 500 μg/kg, we continuously infused esmolol at increasing doses, which were individually titrated for each patient. Mean infusion rates of esmolol were as follows: 40, 75, 140, and 230 μmol/kg per minute. Celiprolol and esmolol induced a comparable dose-dependent decrease in heart rate to a minimum of -10% below baseline. Esmolol caused a significant dose-dependent decrease (-25% below baseline at the highest dose level) in cardiac index (CI). After administration of celiprolol, CI decreased only transiently (-10% below baseline at the second and third dose level) and did not differ from the baseline at the highest dose level. For treatment of severe heart failure, initiation of intravenous β-blocker therapy with low doses of a β 1 -blocker with vasodilating effects may have hemodynamic advantages over conventional β-blockade.Journal of Cardiovascular Pharmacology 10/2001; 38(5):666-671. · 2.29 Impact Factor
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Institutions
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2011
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Medizinische Universität Innsbruck
- Sektion für Genetische Epidemiologie
Innsbruck, Tyrol, Austria
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