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Matthias Lubnow,
Andreas Luchner,
Alois Philipp,
Stefan Buchner, Andreas Jeron,
Christian Karagiannidis,
Thomas Bein,
Michael Pawlik,
Carsten Jungbauer,
Christof Schmid,
Günter A J Riegger,
Michael Pfeifer,
Thomas Müller
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ABSTRACT: The combination of high-frequency oscillatory ventilation (HFOV) and extracorporeal carbon dioxide removal with the interventional lung assist (iLA) in severe acute respiratory distress syndrome (ARDS) represents a novel treatment option.
The study used a retrospective single-center analysis of 21 consecutive adult patients with severe ARDS, ventilated with HFOV/iLA. Efficiency, side effects, and outcome of combined treatment are presented as median (interquartile range).
The following were used to determine patient characteristics: sequential organ failure assessment score, 14; simplified acute physiology score II, 41; and Murray score, 4. The duration of combined treatment was 6 days. The blood flow through the iLA was 1.9 L/min. The Pao(2)/inspired fraction of oxygen ratio increased from 61 (47-86) to 98 (67-116) within 2 hours and to 106 (70-135) mm Hg at 24 hours. Paco(2) decreased from 58 (50-76) to 37 (29-47) mm Hg at 2 hours with normalization of pH 7.28 (7.16-7.36) to 7.43 (7.33-7.49) after 2 hours associated with hemodynamic stabilization. In 6 patients, complications due to iLA treatment were observed, and in 3 patients, complications associated with HFOV were seen. Weaning from HFOV/iLA was successful in 10 patients. The 30-day mortality rate was 43%, and hospital mortality rate was 57%.
The combination of HFOV/iLA is an option in severe pulmonary failure if conventional ventilation fails and pumpdriven extracorporeal membrane oxygenation therapy is not available.
Journal of critical care 09/2010; 25(3):436-44. · 2.13 Impact Factor
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Stefan Buchner,
Kurt Debl,
Stefan Barlage,
Daniel Griese,
Sabine Fredersdorf, Andreas Jeron,
Matthias Lubnow,
Thomas Müller,
Frank Muders,
Stephan Holmer,
Günter A J Riegger,
Andreas Luchner
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ABSTRACT: Whereas N-terminal pro-brain natriuretic peptide (NT-proBNP) is approved for risk stratification of patients with acute coronary syndromes (ACS), short-term temporal changes in NT-proBNP concentrations and the optimal time points for sampling are not clear. The purpose of this study was to better define the short-term changes in NT-proBNP in relation to clinical presentation, reperfusion and prognostic value in patients with ACS, as well as to identify the optimum time points for sampling.
We studied daily plasma concentrations of NT-proBNP in 133 unselected patients with myocardial infarction (n=65), stable coronary artery disease (CAD, n=46) and no CAD (n=22) who underwent coronary angiography.
Patients with non-ST-elevation myocardial infarction (NSTEMI) presented with markedly higher NT-proBNP than patients with ST-elevation myocardial infarction (STEMI) [1305 (741-3208) ng/L vs. 170 (70-424) ng/L, p<0.001]. Also, time to presentation from onset of pain was much longer in NSTEMI as compared to STEMI (>48 h vs. <6 h, p<0.001). Patients with NSTEMI also presented with higher NT-proBNP as compared with CAD [224 (98-732) ng/L] and no CAD [47 (26-102) ng/L; p<0.001, NSTEMI vs. both]. Following successful percutaneous coronary intervention [thrombolysis in myocardial infarction (TIMI) 3-flow established], NT-proBNP increased markedly within 24 h in patients with STEMI [718 (379-1338) ng/L, p<0.01 vs. 0 h], whereas no change in NT-proBNP was noted in patients with NSTEMI [1190 (1010-2024) ng/L, p=0.88 vs. 0 h]. In both STEMI and NSTEMI, NT-proBNP decreased significantly 96 h after successful reperfusion [STEMI -52%, 372 (189-610) ng/L, p<0.05; NSTEMI -52%, 613 (365-724) ng/L, p<0.05]. Unsuccessful reperfusion (TIMI<3) was associated with unchanged or increased NT-proBNP. NT-proBNP at 96 h and peak NT-proBNP further displayed a strong correlation with cardiac troponin T (r=0.64 and r=0.54, p<0.001), a marker of infarct size, and NT-proBNP at 96 h was a strong predictor of long-term prognosis (hazard ratio 7.29, p=0.025).
In patients with NSTEMI, NT-proBNP may be increased as high as concentrations usually associated with acute congestive heart failure despite the absence of clinical signs. In contrast, patients with STEMI and short time to presentation may present with completely normal NT-proBNP, but dramatic short-term increases following reperfusion. NT-proBNP reflects ischemic burden, reperfusion success and prognosis, and the current data support repetitive sampling in patients with ACS.
Clinical Chemistry and Laboratory Medicine 06/2010; 48(6):875-81. · 2.15 Impact Factor
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ABSTRACT: Ablation of atrial fibrillation (AF) has been one of the most difficult and time-consuming electrophysiological procedures. Due to the rapidly increasing demand for ablation procedures, technical advances would be helpful to reduce complexity and procedure time in AF ablation. Therefore, we investigated the feasibility of a single-catheter technique for pulmonary vein (PV) isolation utilizing a decapolar catheter combined with a duty-cycled, unipolar-bipolar radiofrequency (RF) generator.
AF mapping and ablation was performed in 21 consecutive patients (mean age 59 +/- 12 years, 9 males) with paroxysmal AF (n = 17) and persistent AF (n = 4). The ablation catheter was forwarded to the LA via single-transseptal puncture. All electrodes were energized in 2 to 5 applications per vein, followed by segmental RF applications, as needed, to achieve electrical isolation. To assess left atrial anatomy for purposes of catheter manipulation, and later evaluate the possibility of asymptomatic PV-stenosis, CT or MR imaging was performed both prior to ablation and at 6-month follow-up.
Isolation could be achieved in 85/86 veins (99%). Procedure time for ablation was 81 +/- 13 minutes, and fluoroscopy time was 30 +/- 11 minutes. There were no procedural complications. Success rate at 6 months was 86% (18/21). MR or CT imaging excluded asymptomatic PV-stenosis.
Mapping and ablation of PVs can be performed in a safe and efficient manner using a single-catheter technique, with short procedure times and minimal learning curve. Thus, this system may be of high interest not only for high volume but all centers performing AF ablation.
Journal of Cardiovascular Electrophysiology 07/2009; 20(10):1097-101. · 3.06 Impact Factor
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Kamil Sedlacek,
Klaus Stark,
Shane R Cunha,
Arne Pfeufer,
Stefan Weber,
Iris Berger,
Siegfried Perz,
Stefan Kääb,
Hans-Erich Wichmann,
Peter J Mohler,
Christian Hengstenberg, Andreas Jeron
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ABSTRACT: Spatial and timely variations in QT interval, even within its normal range, may underlie susceptibility to cardiac arrhythmias and sudden cardiac death. Given its important role in cardiac electrophysiology, we hypothesized that common genetic variation in ankyrin-B gene (ANK2) might modify QT interval length.
The study population consisted of 1188 participants of the World Health Organizational Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO MONICA) general population survey Cooperative Health Research in the Region of Augsburg (KORA S3). Corrected QT interval was calculated using population specific linear regression formulas. A total of 22 single-nucleotide polymorphisms in the genomic region of ANK2 gene were genotyped using TaqMan technology. In a replication study, 6 single nucleotide polymorphisms were genotyped in 3890 individuals from a second population study (KORA S4). The rare variant of the single-nucleotide polymorphism rs6850768 (allele frequency, 0.28) significantly influenced duration of the QT interval, both in KORA S3 and KORA S4 populations. In homozygotes, the shortening of the QT interval was 3.79 ms (95% CI, 1.48 to 5.58; P=0.001 and P=0.0008 for log-additive and dominant model, respectively) in KORA S3 and 2.94 ms (95% CI, 1.11 to 4.77; P=0.001 and P=0.006 for log-additive and dominant genetic model, respectively) in KORA S4. A common 2-locus haplotype (rs11098171-rs6850768; population frequency, 28%) was associated with a QT interval difference of 2.85 ms (permutation; P=0.006) in KORA S3 and 1.23 ms (permutation; P=0.009) in KORA S4. Reverse transcription-polymerase chain reaction expression analysis of the human ANK2 5' genomic region in the human left ventricular tissue revealed 2 previously unidentified ANK2 5' exons in the proximity of the identified variants.
Common genetic variants juxtaposed with novel exons in the distant 5' genomic region of ANK2 influence the QT interval length in the general population. These findings support the role of ankyrin-B in normal cardiac electric activity.
Circulation Cardiovascular Genetics 12/2008; 1(2):93-9. · 6.11 Impact Factor
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Wibke Reinhard,
Klaus Stark,
Katharina Neureuther,
Kamil Sedlacek,
Marcus Fischer,
Andrea Baessler,
Stefan Weber,
Bernhard Kaess,
Silke Wiedmann,
Jeanette Erdmann,
Wolfgang Lieb, Andreas Jeron,
Guenter Riegger,
Christian Hengstenberg
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ABSTRACT: Myocardial infarction (MI) is a complex disease. Multiple genes and their interaction with various environmental factors influence the pathogenesis of MI that is thought to be tightly regulated by inflammatory pathways. Recent progress in genetic analysis includes the use of large-scale genome-wide association studies that have proven to be powerful tools even in the analysis of multifactorial phenotypes. However, certain genes are only sparsely represented on the available gene chips and additional candidate gene approaches are necessary. One such example is the CNR2 gene, encoding the cannabinoid receptor 2 (CB2), which has been implicated in mediating anti-inflammatory and anti-atherosclerotic effects in vivo. We therefore hypothesized that genetic variations within the CNR2 gene are associated with the development of MI or classic cardiovascular risk factors. In a large case-control study, 1,968 individuals from the German MI family study were examined with 13 single nucleotide polymorphisms (SNPs) covering CNR2 and the adjacent genes. The association of these SNPs with MI or cardiovascular risk factors, such as arterial hypertension, obesity, hypercholesterolemia and diabetes mellitus, was determined. In allelic and genotypic models, none of the SNPs showed a significant association with MI. Separate analyses for men and women revealed no gender-specific relationship between common genetic variations within the CNR2 gene and MI. Moreover, no significant association between CNR2 gene variants and common cardiovascular risk factors was observed. We therefore provide evidence in a large German population that common polymorphisms within the CNR2 gene confer no susceptibility to MI or to cardiovascular risk factors.
International Journal of Molecular Medicine 08/2008; 22(2):165-74. · 1.98 Impact Factor
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EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 06/2008; 4(1):158-60. · 3.29 Impact Factor
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Wibke Reinhard,
Klaus Stark,
Kamil Sedlacek,
Marcus Fischer,
Andrea Baessler,
Katharina Neureuther,
Stefan Weber,
Bernhard Kaess,
Silke Wiedmann,
Stefan Mitsching,
Wolfgang Lieb,
Jeanette Erdmann,
Christa Meisinger,
Angela Doering,
Ralf Tolle, Andreas Jeron,
Guenter Riegger,
Christian Hengstenberg
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ABSTRACT: PPARalpha (peroxisome-proliferator-activated receptor alpha) regulates the expression of genes that are involved in lipid metabolism, tissue homoeostasis and inflammation. Consistent rodent and human studies suggest a link between PPARalpha function and cardiovascular disease, qualifying PPARalpha [PPARA in HUGO (Human Genome Organisation) gene nomenclature] as a candidate gene for coronary artery disease. In the present study, we comprehensively evaluated common genetic variations within the PPARalpha gene and assessed their association with myocardial infarction. First, we characterized the linkage disequilibrium within the PPARalpha gene in an initial case-control sample of 806 individuals from the Regensburg Myocardial Infarction Family Study using a panel of densely spaced SNPs (single nucleotide polymorphisms) across the gene. Single SNP analysis showed significant association with the disease phenotype [OR (odds ratio)=0.74, P=0.012, 95% CI (confidence interval)=0.61-0.94 for rs135551]. Moreover, we identified a protective three-marker haplotype with an association trend for myocardial infarction (OR=0.76, P=0.067, 95% CI=0.56-1.02). Subsequently, we were able to confirm the single SNP and haplotype association results in an independent second case-control cohort with 667 cases from the Regensburg Myocardial Infarction Family Study and 862 control individuals from the WHO (World Health Organization) MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) Augsburg project (OR=0.87, P=0.046, 95% CI=0.72-0.99 for rs135551 and OR=0.80, P=0.034, 95% CI=0.65-0.98 for the three-marker haplotype respectively). From these cross-sectional association results, we provide evidence that common variations in the PPARalpha gene may influence the risk of myocardial infarction in a European population.
Clinical Science 04/2008; 115(10):301-8. · 4.61 Impact Factor
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Klaus Stark,
Katharina Neureuther,
Kamil Sedlacek,
Wibke Hengstenberg,
Marcus Fischer,
Andrea Baessler,
Silke Wiedmann, Andreas Jeron,
Stephan Holmer,
Jeanette Erdmann,
Heribert Schunkert,
Christian Hengstenberg
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ABSTRACT: Recently, the genetic variant Y402H in the CFH (complement factor H) gene was associated with an increased risk for MI (myocardial infarction) in a prospective Caucasian cohort. In another nested case-control study, however, the CFH-Y402H variant did not carry susceptibility to MI. The aim of the present study was to test for an association between the CFH-Y402H variant and MI in a large case-control sample with a familial background for CAD (coronary artery disease). A total of 2161 individuals from the German MI family study were studied by questionnaire, physical examination and biochemical analyses. MI patients (n=1188; 51.4+/-8.6 years at first MI) were recruited from families with at least two members affected by MI and/or severe CAD. Spouses, sisters-in-law and brothers-in-law respectively, without MI/CAD were included as unaffected controls (n=973; 56.9+/-9.8 years). Genotyping was performed using a TaqMan assay. The common Y402H variant in the CFH gene was not associated with classical cardiovascular risk factors (diabetes, hypercholesterolaemia, hypertension, obesity, smoking and C-reactive protein serum levels). No association was found between the CFH-Y402H variant and susceptibility to MI. Separate analyses in both men and women revealed no gender-specific influence of the gene variant on cardiovascular risk factors or MI. This investigation was unable to replicate the association between the common CFH-Y402H variant and susceptibility to MI in our large Caucasian population which is enriched for genetic factors. We conclude that the CFH-Y402H variant has no relevant risk-modifying effect in our population.
Clinical Science 09/2007; 113(4):213-8. · 4.61 Impact Factor
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ABSTRACT: A 28-year-old female with corrected anomalous pulmonary venous drainage presented with multiple atrial arrhythmias many years later. Ablation techniques eliminated most of the arrhythmias except atrial tachycardia with 1:1 AV conduction. A dual-chamber pacemaker with antiatrial tachycardia features was implanted and was shown to be effective in arrhythmia control when the standard algorithm was overridden by an external patient activation device.
Europace 07/2006; 8(6):413-5. · 1.98 Impact Factor
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ABSTRACT: The heart rate turbulence (HRT) parameters were introduced for risk stratification of ventricular arrhythmias in postmyocardial infarction patients. However, the relationship of these parameters with other risk stratificators such as heart rate variability (HRV), repolarization parameters or left ventricular function is unknown. Furthermore, the influence of age and medication on HRT remains to be evaluated. Holter ECG's of 509 post-MI patients (1-10 years after MI) were screened for single ventricular extrasystole. In 196 patients the parameters' turbulence onset (TO) and turbulence slope (TS) could be computed. A pathological TO (>0%) and TS (<2.5 ms) was found in 58 and 54 patients, respectively. HRT was not related to gender, but was correlated with age (TS: r = 0.209, P < 0.01). No relationship was observed between QT interval, QTc interval or QT dispersion and HRT parameters. Individuals with a pathological HRT showed decreased HRV values (e.g., PNN50: 2.8 vs. 11.5; P < 0.001). Of all MI patients with systolic left ventricular dysfunction (EF < 45%, n = 46), 18 showed a pathological TO (39%) compared to 34 out of 142 patients (24%) with an EF > 45%. In contrast, the percentage of pathological HRT was not different between patients with left ventricular hypertrophy (16 out of 59, 27%) compared to patients without LVH (38 out of 133, 28%). The HRT was pathological in 14 out of 24 patients with diabetes mellitus (58%) compared to 40 out of 172 (23%) normoglycemic patients (TO: -0.6 +/- 3.1 vs. -2.5 +/- 5.5, P < 0.02). HRT was similar in patients with ss-blockers (n = 96) as in patients without ss-blockers (n = 100). In stable post-MI patients, HRT is influenced by age and left ventricular function and correlates with heart rate variability. Therapy with ss-blockers has no influence on HRT, while diabetic patients may have an increased likelihood of pathological HRT.
Annals of Noninvasive Electrocardiology 10/2003; 8(4):296-301. · 1.10 Impact Factor
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Connie R Bezzina,
Arie O Verkerk,
Andreas Busjahn, Andreas Jeron,
Jeanette Erdmann,
Tamara T Koopmann,
Zahurul A Bhuiyan,
Ronald Wilders,
Marcel M A M Mannens,
Hanno L Tan,
Friedrich C Luft,
Heribert Schunkert,
Arthur A M Wilde
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ABSTRACT: Genetic variants of cardiac ion channels may influence cardiac repolarization. Thereby such variants may modulate the penetrance of primary electrical disorders, contribute to differences in susceptibility to drug-induced QT-prolongation between individuals, or contribute to rhythm disturbances in the context of structural heart disease. Since the current encoded by KCNH2 (HERG; I(Kr)) is a primary determinant of repolarization, we conducted association studies between the respective alleles of the common amino acid-changing polymorphism at codon 897 (2690A>C; K897T) within HERG and rate-corrected QT interval (QTc).
Association analysis in Caucasian subjects (n=1030) revealed a significant association of this polymorphism with QTc (P=0.0025) with CC homozygotes having a significantly shorter QTc (388.5+/-2.9 ms) compared to AA homozygotes (398.5+/-0.9) and heterozygotes (AC, 397.2+/-1.2). The latter two genotypes were associated with comparable mean QTc's, suggesting that the 2690C-allele is recessive. After stratification by sex, the polymorphism was more predictive of QTc in females (P=0.0021), a finding that was replicated in a second population sample (n=352) from the same ethnic background (P=0.044). To assess whether this polymorphism could represent a 'functional' polymorphism, we compared the biophysical properties of K897- and T897-HERG channels by whole-cell voltage clamp. Compared to the K897 channel, the T897 channel displayed a shift of -7 mV in voltage dependence of activation and increased rates of current activation and deactivation.
As confirmed in modeling studies, these changes are expected to shorten action potential duration by an increase in I(Kr). This recapitulates the shorter QTc in females homozygous for the 2690C-allele.
Cardiovascular Research 08/2003; 59(1):27-36. · 6.06 Impact Factor
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ABSTRACT: Interleukin-6 (IL-6) is expressed in the myocardium and has been implicated in cell proliferation, negative inotropic effects and myocardial hypertrophy. To determine whether myocardial IL-6 is modified by neurohumoral and immunoregulatory stimuli, we studied the effects of lipopolysaccharide (LPS), corticosterone (CS), isoproterenol and angiotensin II on myocardial IL-6 secretion in superfused myocardium.
Slices of rat left ventricular myocardium were superfused in 80 microl chambers for up to 5h. LPS (1, 50, and 100 microg/ml), CS (10(-7), 10(-6), and 10(-5)M, DSMO as vehicle), isoproterenol (10(-6), 10(-7), and 10(-8)M) and angiotensin II (10(-5), 10(-7), and 10(-9)M) were added to the culture medium at hour 2. IL-6 was measured in the perfusate by ELISA.
Physiological corticosterone concentrations (10(-7)M) resulted in an increase in IL-6 concentration (142%) while high doses of steroid decreased IL-6 significantly (CS 10(-6)M: 88+/-14%,p<.05; CS 10(-5): 91+/-9%,p<.05) after 5h. Left ventricular IL-6 secretion was significantly stimulated by LPS 50 microg/ml (3262+/-1684% vs. CTRL: 116+/-34%, p<.01). Isoproterenol treatment increased in IL-6 secretion compared to controls with and without CS, while angiotensin II reduced IL-6 concentration only in combination with CS.
Myocardial IL-6 secretion is modulated by physiological concentrations of corticosterone or angiotensin II and can be induced by LPS or isoproterenol, indicating a tight regulation of this cytokine. Suppression of cytokine expression within the heart might be a potential therapeutic goal in the treatment of various cardiovascular diseases.
Brain Behavior and Immunity 08/2003; 17(4):245-50. · 4.72 Impact Factor
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ABSTRACT: Activation of cytokines such as interleukin-6 (IL-6) has been implicated in the pathogenesis of left ventricular dysfunction and hypertrophy since they have been shown to mediate cell proliferation, negative inotropic effects and myocardial hypertrophy. However, the effects of immunosuppressive therapy on cytokines in the treatment of heart failure and hypertrophy are unclear.
To test the hypothesis that systemic immunosuppresion may influence serum and myocardial IL-6 and, thereby, may affect progression of myocardial hypertrophy. We studied the effects of chronic treatment with methotrexate (MTx) and with the ACE inhibitor ramipril on IL-6 in rats with pressure overload left ventricular hypertrophy (LVH) due to aortic banding.
Animals were treated with either vehicle (n = 6) or methotrexate (MTx 1: 0.3 mg/kg BW/week; MTx 2: 0.9 mg/kg BW/week; i.p.; n = 6 each group) once a week during weeks 4-12 after aortic banding; sham-operated rats served as controls (CTRL; n = 8). During the development of LVH, serum IL-6 was determined by rat-specific ELISA and 12 weeks after aortic banding myocardial IL-6 was measured using a tissue superfusion technique or determining of protein concentration.
Aortic banding significantly lowered blood pressure, increased left ventricular weight and resulted in elevated serum IL-6 levels (27.6 +/- 5.1 vs 19.1 +/- 2.3 pg/ml, p < 0.05) compared to CTRL. MTx treatment normalised the initially elevated serum IL-6 levels after 8 weeks of treatment. The significant increase in IL-6 concentration in the superfusate of all aortic banding groups compared to CTRL (< 30%, p < 0.05) was not altered by prior MTx therapy. Accordingly, both doses of MTx failed to prevent LVH progression (1.67 +/- 0.23 g vs. 2.32 +/- 0.31 g, p < 0.05). In contrast, chronic inhibition of the RAAS not only prevents LVH but also reduces myocardial IL-6 concentration (6898 +/- 355 vs. 3073 +/- 366 pg/mg protein, p < 0.05).
Pressure overload LVH in rats is characterized by an increase in serum levels of IL-6 as well as myocardial IL-6. Chronic immunosuppressive therapy normalized systemic IL-6 levels, but failed to reduce cardiac IL-6 expression and the progression of LVH, while ACE inhibition is sufficient to modify LVH and thereby normalises myocardial IL-6 expression.
Immunobiology 04/2002; 205(1):51-60. · 3.20 Impact Factor
