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Helmut Drexler

Publications and source records attributed to Helmut Drexler.

At least 19 recordsLinked to original sources
PubMed2006

Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay.

BACKGROUND: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor beta (TGF-beta) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. METHODS: We developed an IRMA that uses a polyclonal, affinity chromatography-purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). RESULTS: The assay had a detection limit of 20 ng/L, an intraassay imprecision of < or =10.6%, and an interassay imprecision of < or =12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-beta. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly individuals presented with a median GDF15 concentration of 762 ng/L (25th-75th percentiles, 600-959 ng/L). GDF15 concentrations were associated with age and with cystatin C and C-reactive protein concentrations. CHF patients had increased GDF15 concentrations that were closely related to disease severity. CONCLUSION: The IRMA can detect GDF15 in human serum and plasma with excellent sensitivity and specificity. The reference limits and confounding variables defined for apparently healthy elderly individuals and the favorable preanalytic characteristics of GDF15 are expected to facilitate future studies of GDF15 as a biomarker in various disease settings, including CHF.

Adult↗
PubMed2006

Angiotensin II type 1-receptor antagonism prevents type IIA secretory phospholipase A2-dependent lipid peroxidation.

Accumulation and modification of low density lipoproteins (LDL) within the vessel wall represent key events in atherogenesis. Secretory phospholipase A2 type IIA (sPLA2-IIA) modulates the enzymatic process of LDL-modification and was recently identified as an independent predictor of coronary events in patients with coronary artery disease (CAD). Angiotensin II (ANG II) type 1 (AT1)-receptor blockade reduces LDL-modification and atherosclerotic plaque formation in rodent and primate models of atherosclerosis. Therefore, we assessed whether ANG II via its AT1-receptor enhances sPLA2-IIA-dependent lipid peroxidation in vitro and in patients with CAD. Stimulation of rat aortic smooth muscle cells with ANG II (10(-7) mol/L) enhanced sPLA2-IIA protein expression, activity as well as LDL-peroxidation, determined by western blot, activity assay and malondialdehyde (MDA)-assay and diene formation, respectively, and were blunted by AT1-receptor blockade (Losartan, 10(-5) mol/L). In addition, ANG II-induced sPLA2 activity and LDL-peroxidation were abolished by the sPLA2-IIa activity inhibitor LY311727 (10(-5) mol/L). To evaluate a potential clinical implication, patients (n=18) with angiographically documented CAD were treated with the AT1-receptor blocker Irbesartan (IRB; 300 mg/d) for 12 weeks. Blood samples were obtained from patients pre- and post-treatment and from healthy volunteers. SPLA2-IIA serum level and activity, circulating antibodies against oxidized LDL (oxLDL), oxLDL and MDA were determined in patients and found to be significantly increased compared to healthy volunteers. IRB therapy reduced these markers of inflammation, whereas total cholesterol, HDL- and LDL-fractions remained unchanged. ANG II may elicit pro-atherosclerotic effects via type IIA sPLA2-dependent LDL-modifications. Chronical AT1-receptor blockade reduces sPLA2-IIA level and activity and subsequently lipid peroxidation. Theses findings represent a novel anti-atherosclerotic mechanism and imply that AT1-receptor blockade elicits anti-atherosclerotic potencies even in the absence of plasma cholesterol reduction.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Pregnancy in a Marfan patient with pre-existing aortic dissection.

In women with Marfan syndrome pregnancy increases the risk of aortic dissection. There are a number of articles reporting the outcome of acute aortic dissection during pregnancy in this patient group. In contrast, only scarce information is available concerning pregnancy in patients with pre-existing chronic aortic dissection. We report the case of a pregnant Marfan syndrome patient with pre-existing chronic aortic dissection that showed a favourable maternal and fetal outcome.

Adult↗
PubMed2006

EuroHeart Failure Survey II (EHFS II): a survey on hospitalized acute heart failure patients: description of population.

AIMS: The objective of the EuroHeart Failure Survey II (EHFS II) was to assess patient characteristics, aetiology, treatment, and outcome of acute heart failure (AHF) in Europe in relation to the guidelines on the diagnosis and treatment of AHF published by the European Society of Cardiology. METHODS AND RESULTS: Patients hospitalized for AHF were recruited by 133 centres in 30 European countries. Three thousand five hundred and eighty patients were entered into the database by the end of August 2005. Mean age was 70 years, and 61% of patients were male. New-onset AHF (de novo AHF) was diagnosed in 37%, of which 42% was due to acute coronary syndromes (ACS). Clinical classification according to the guidelines divided AHF patients into (i) decompensated HF (65%), (ii) pulmonary oedema (16%), (iii) HF and hypertension (11%), (iv) cardiogenic shock (4%), and (v) right HF (3%). Coronary heart disease, hypertension, and atrial fibrillation were the most common underlying conditions. Arrhythmias, valvular dysfunction, and ACS were each present as precipitating factor in one-third of cases. Preserved left ventricular ejection fraction (> or =45%) was observed in 34%. Valvular disorders were common, especially mitral regurgitation (MR) which was reported on echocardiography in 80% of patients. Median length of stay was 9 days, and in-hospital mortality 6.7%. At discharge, 80% of patients were on angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers, whereas 61% were taking beta-blocker medication. CONCLUSION: Decompensated HF is the most common clinical presentation of AHF patients. More than one-third of AHF patients do not have a previous history of HF, and new-onset HF is often caused by ACS. Preserved systolic function is found in a substantial proportion of the patients. The prevalence of valvular dysfunction is strikingly high and contributes to the clinical presentation. The EHFS II on AHF verified that the use of evidence-based HF medication was well adopted to clinical practice.

Acute Disease↗
PubMed2006

cGMP-dependent protein kinase type I inhibits TAB1-p38 mitogen-activated protein kinase apoptosis signaling in cardiac myocytes.

Cardiac myocyte apoptosis during ischemia and reperfusion (I/R) is tightly controlled by a complex network of stress-responsive signaling pathways. One pro-apoptotic pathway involves the interaction of the scaffold protein TAB1 with p38 mitogen-activated protein kinase (p38 MAPK) leading to the autophosphorylation and activation of p38 MAPK. Conversely, NO and its second messenger cGMP protect cardiac myocytes from apoptosis during I/R. We provide evidence that the cGMP target cGMP-dependent protein kinase type I (PKG I) interferes with TAB1-p38 MAPK signaling to protect cardiac myocytes from I/R injury. In isolated neonatal cardiac myocytes, activation of PKG I inhibited the interaction of TAB1 with p38 MAPK, p38 MAPK phosphorylation, and apoptosis induced by simulated I/R. During I/R in vivo, mice with a cardiac myocyte-restricted deletion of PKG I displayed a more pronounced interaction of TAB1 with p38 MAPK and a stronger phosphorylation of p38 MAPK in the myocardial area at risk during reperfusion and more apoptotic cardiac myocytes in the infarct border zone as compared with wild-type littermates. Notably, adenoviral expression of a constitutively active PKG I mutant truncated at the N terminus(PKGI-DeltaN1-92) did not inhibit p38 MAPK phosphorylation and apoptosis induced by simulated I/R in vitro, indicating that the N terminus of PKG I is required. As shown by co-immunoprecipitation experiments in HEK293 cells, cGMP-activated PKG I, but not constitutively active PKG I-DeltaN1-92 or PKG I mutants carrying point mutations in the N-terminal leucine-isoleucine zipper, interacted with p38 MAPK, and prevented the binding of TAB1 to p38 MAPK. Together, our data identify a novel interaction between the cGMP target PKG I and the TAB1-p38 MAPK signaling pathway that serves as a defense mechanism against myocardial I/R injury.

Adenoviridae↗
PubMed2006

Inflammatory, abscess-forming foreign body reaction mimics a thrombus formation on an atrial septal defect closure device: A commented case report.

We are presenting a case of floating left and right atrial formations on an atrial septal defect occluder system (23mm StarFLEX)-Occluder) initially supposed to be thrombotic appositions in a 57-year-old man. The closure was performed on the background of left hemispheric stroke and atrial septal aneurysm (ASA) with patent foramen ovale (PFO). The suspect structures were detected in the 6-month follow-up by transesophageal echocardiography (TEE). The patient underwent a successful surgical explantation of the closure device and closure of the patent foramen ovale (PFO) using a pericardial patch. The pathological evaluation of the biatrial device associated appositions revealed hytrophic heart muscle tissue with perifocal scarring and purulent abscess-forming, granulating and foam-cell including inflammatory foreign body reaction instead of the expected thrombus formation.

Abscess↗
PubMed2006

Critical role for p47phox in renin-angiotensin system activation and blood pressure regulation.

OBJECTIVE: Renin-angiotensin system (RAS) activation leads to increased production of NAD(P)H oxidase-derived reactive oxygen species (ROS), and both have been implicated in the initiation and progression of arterial hypertension, atherosclerosis, and cardiac hypertrophy. The cytosolic subunit p47phox is critically involved in agonist-induced NAD(P)H oxidase activation. Here, we investigated the role of p47phox in blood pressure control, endothelium-dependent relaxation, cardiac hypertrophy, RAS activation, and renal oxidative stress under resting conditions. METHODS AND RESULTS: Mice deficient in p47phox (on C57BL/6 background) developed significantly higher systolic blood pressure levels compared to C57BL/6 wild-type animals (136.0+/-3.0 mmHg vs. 112.2+/-2.6, P<0.01, n=16) as measured by the tail cuff method from week 6 up to week 12 post partum. The increase in blood pressure in p47phox-/- mice was associated with an impaired endothelium-dependent relaxation (P<0.005 vs. wild-type, n=11). At the age of 12 weeks p47phox-/- mice showed increased plasma renin activity as analyzed by radioimmunoassay (14.5+/-1.8 ng/mL/h vs. 9.6+/-1.7 ng/mL/h, P<0.05, n=10) and enhanced angiotensin converting enzyme (ACE) activity in the kidney and aorta as measured by Hip-His-Leu cleavage (7.6+/-0.8 vs. 4.8+/-0.9 nmol/L His-Leu/mg protein, P<0.05, n=5) compared to wild-type mice. No differences in oxygen radical formation was determined in kidney samples by lucigenin- and luminol-enhanced chemiluminescence or by electron spin resonance spectroscopy. Consistently, treatment with the radical scavenger tempol did not lower blood pressure in p47phox-/- mice, whereas ACE and angiotensin II type I receptor inhibition normalized blood pressure. CONCLUSION: Deficiency of the NAD(P)H oxidase subunit p47phox leads to RAS activation, which subsequently contributes to blood pressure increase in a ROS-independent manner.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Transcoronary delivery of bone marrow cells to the infarcted murine myocardium: feasibility, cellular kinetics, and improvement in cardiac function.

Efficient strategies for labelling and delivery of bone marrow derived stem cells (BMCs) are required to elucidate the cellular kinetics and therapeutic effects after BMC transfer for myocardial infarction (MI). Lineage negative (lin-) BMCs, labelled ex vivo in a simple procedure with the cell tracker dye tetramethyl-rhodamine (TAMRA), were reliably detected by fluorescence microscopy with higher specificity than retroviral enhanced green fluorescence protein (EGFP) marking and detection. Only few cells entered the ischemic myocardium after intravenous (i.v.) application, but this number increased more than 18-fold after transcoronary delivery. Time course and kinetic analysis over 12 h revealed that myocardial colonization seems to be a biphasic process of first order decay with different elimination half-lives. Most cells are eliminated rapidly during the first 2 h (t1/2 40 min), but the remaining cells are retained significantly longer in the ischemic heart (t1/2 5.2 h). In contrast, BMC colonization of the spleen increased rather in a linear fashion. Although transcoronary BMC transfusion did not alter infarct size, it increased capillary density in the infarct border zone and improved LV function 4 weeks after MI. In conclusion, BMCs delivered by transcoronary injection increase capillary density and improve LV function after MI although homing to the ischemic heart is only transient.

Animals↗
PubMed2006

The consensus of the task force of the European Society of Cardiology concerning the clinical investigation of the use of autologous adult stem cells for repair of the heart.

A task force has been established by the European Society of Cardiology to investigate the role of progenitor/stem cell therapy in the treatment of cardiovascular disease. This article is the consensus of this group, of what clinical studies are needed in this field, and the challenges to be addressed in the translation of progenitor/stem cell biology to repair of the heart.

Adult Stem Cells↗
PubMed2006

JunD attenuates phenylephrine-mediated cardiomyocyte hypertrophy by negatively regulating AP-1 transcriptional activity.

OBJECTIVE: Mice deficient for the AP-1 transcription factor JunD, the only Jun protein constitutively expressed and clearly detectable in the mammalian heart, develop enhanced cardiac hypertrophy in response to chronic pressure overload. Catecholamines inducing alpha-adrenergic receptor-mediated signaling have been implicated in the neurohumoral response to pressure overload and the development of left ventricular hypertrophy. In the present study we analyzed the mechanistic role of JunD in cardiomyocyte hypertrophy in vitro in response to alpha-adrenergic agonist phenylephrine (PE). METHODS: Cardiomyocytes were isolated from 1- to 3-day-old rats and transfected with adenoviruses expressing LacZ or wild-type JunD, or with expression vectors encoding LacZ, wild-type JunD, mutated JunD forming only JunD homodimers (JunDeb1), mutated JunD lacking the JNK site (JunD-Delta 162), or c-Jun. After stimulation with PE (10(-5) mol/L), hypertrophic growth of cardiomyocytes (cross-sectional area and [3H]-leucine incorporation) and mRNA expression of JunD, c-Jun, c-Fos, and atrial natriuretic peptide (ANP) were analyzed. Transcriptional activation was determined by luciferase activity in cardiomyocytes transfected with AP-1 or ANP luciferase reporter plasmids. Gel shift assays with an AP-1 consensus oligonucleotide were performed to analyze AP-1 DNA binding activities. RESULTS: PE augmented mRNA levels of c-Jun and c-Fos, but decreased JunD transcript levels. Adenoviral over-expression of wild-type JunD blunted PE-induced hypertrophic growth and expression of ANP mRNA. Over-expression of JunD in cardiomyocytes caused enhanced AP-1 protein-DNA binding, without increasing the transcriptional response from AP-1 or ANP luciferase reporter plasmids at baseline or upon PE stimulation. Moreover, over-expression of JunDeb1 attenuated transcription from AP-1 or ANP luciferase reporter plasmids and blunted c-Jun-mediated acceleration of AP-1 transcriptional activity at baseline and in response to PE. CONCLUSIONS: Our observations establish a novel role for JunD as a negative regulator of cardiomyocyte hypertrophy in response to hypertrophic stimuli by inhibiting AP-1 transcriptional activity.

Adrenergic alpha-Agonists↗
PubMed2006

Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months' follow-up data from the randomized, controlled BOOST (BOne marrOw transfer to enhance ST-elevation infarct regeneration) trial.

BACKGROUND: Intracoronary transfer of autologous bone marrow cells (BMCs) may enhance recovery of left ventricular (LV) function in patients after acute myocardial infarction (AMI). However, clinical studies addressing the effects of BMCs after AMI have covered only limited time frames ranging from 3 to 6 months. The critical question of whether BMC transfer can have a sustained impact on LV function remains unanswered. METHODS AND RESULTS: After percutaneous coronary intervention with stent implantation (PCI) of the infarct-related artery, 60 patients were randomized 1:1 to a control group with optimal postinfarction therapy and a BMC transfer group that also received an intracoronary BMC infusion 4.8+/-1.3 days after PCI. Cardiac MRI was performed 3.5+/-1.5 days, 6+/-1 months, and 18+/-6 months after PCI. BMC transfer was not associated with adverse clinical events. In the control group, mean global LV ejection fraction increased by 0.7 and 3.1 percentage points after 6 and 18 months, respectively. LV ejection fraction in the BMC transfer group increased by 6.7 and 5.9 percentage points. The difference in LVEF improvement between groups was significant after 6 months but not after 18 months (P=0.27). The speed of LV ejection fraction recovery over the course of 18 months was significantly higher in the BMC transfer group (P=0.001). CONCLUSIONS: In this study, a single dose of intracoronary BMCs did not provide long-term benefit on LV systolic function after AMI compared with a randomized control group; however, the study suggests an acceleration of LV ejection fraction recovery after AMI by BMC therapy.

Adult↗
PubMed2006

Impact of intracoronary bone marrow cell transfer on diastolic function in patients after acute myocardial infarction: results from the BOOST trial.

AIMS: We have recently shown in the randomized-controlled BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial that intracoronary autologous bone marrow cell (BMC) transfer improves left ventricular (LV) ejection fraction recovery in patients after acute myocardial infarction (AMI). However, the impact of BMC therapy on LV diastolic function in patients after AMI has remained uncertain. METHODS AND RESULTS: Using (tissue) Doppler echocardiography, we evaluated the effects of BMC transfer on LV diastolic function in patients enrolled in the BOOST trial. After successful primary percutaneous coronary intervention (PCI) for acute ST-elevation myocardial infarction (MI), patients were randomized to a control (n = 29) or BMC transfer group (n = 30). Diastolic function was determined 4.5+/-1.5 days after PCI, at 6 months, and at 18 months by measuring transmitral flow velocities (E/A ratio), diastolic myocardial velocities (Ea/Aa ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). All analyses were performed in a blinded fashion. There was an overall effect of BMC transfer on E/A [0.33+/-0.12; 95% confidence interval (CI): 0.09-0.57; P = 0.008] and Ea/Aa ratios (0.29+/-0.14; 95% CI: 0.01-0.57; P = 0.04). In contrast, we found no effect of BMC transfer on DT (-5+/-14 ms; 95% CI: -33 to 22; P = 0.70), IVRT (-7+/-7 ms; 95% CI: -20 to 6; P = 0.29), and E/Ea ratio (0.35+/-0.14; 95% CI: -0.92 to 1.62; P = 0.57). CONCLUSION: Intracoronary autologous BMC transfer improves echocardiographic parameters of diastolic function in patients after AMI.

Bone Marrow Cells↗
PubMed2006

Combined aspirin and clopidogrel resistance associated with recurrent coronary stent thrombosis.

We report about a 72-year-old woman who was admitted to our hospital because of an acute ST-elevation myocardial infarction (STEMI). At admission, she received a loading dose of 300 mg Clopidogrel and 500 mg aspirin (ASA) prior to angioplasty with stenting of a 90% diameter stenosis of the proximal right coronary artery. After intervention, 75 mg Clopidogrel and 300 mg ASA OD were continued. Three days later, she developed a recurrent acute STEMI due to stent thrombosis and a second stent implantation was performed. The dose of Clopidogrel and ASA remained unchanged. Three days later, the patient suffered a third STEMI due to a restent thrombosis and additional stent implantation was performed. The dose of Clopidogrel and ASA was increased to 75 mg BD and 500 mg OD. Platelet function analysis and aggregation studies demonstrated dose-independent ASA resistance. ADP-induced aggregation showed a short-term platelet inhibition with subsequent rapid normalisation, thus suggesting Clopidogrel resistance. Therefore, the treatment was changed to coumadin and ASA 100 mg OD. Since then, the patient has been clinically stabile. Our case indicates for the first time the existence of a subgroup of patients with combined Clopidogrel and ASA resistance. We conclude that identification of these patients is required and alternative therapeutic options have to be considered.

Aged↗
PubMed2006

The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury.

Data from the Women's Health Study show that serum levels of growth-differentiation factor-15 (GDF-15), a distant member of the transforming growth factor-beta superfamily, are an independent risk indicator for adverse cardiovascular events. However, the cellular sources, upstream regulators, and functional effects of GDF-15 in the cardiovascular system have not been elucidated. We have identified GDF-15 by cDNA expression array analysis as a gene that is strongly upregulated by nitrosative stress in cultured cardiomyocytes isolated from 1- to 3-day-old rats. GDF-15 mRNA and pro-peptide expression levels were also induced in cardiomyocytes subjected to simulated ischemia/reperfusion (I/R) via NO-peroxynitrite-dependent signaling pathways. GDF-15 was actively secreted into the culture supernatant, suggesting that it might exert autocrine/paracrine effects during I/R. To explore the in vivo relevance of these findings, mice were subjected to transient or permanent coronary artery ligation. Myocardial GDF-15 mRNA and pro-peptide abundance rapidly increased in the area-at-risk after ischemic injury. Similarly, patients with an acute myocardial infarction had enhanced myocardial GDF-15 pro-peptide expression levels. As shown by immunohistochemistry, cardiomyocytes in the ischemic area contributed significantly to the induction of GDF-15 in the infarcted human heart. To delineate the function of GDF-15 during I/R, Gdf-15 gene-targeted mice were subjected to transient coronary artery ligation for 1 hour followed by reperfusion for 24 hours. Gdf-15-deficient mice developed greater infarct sizes and displayed more cardiomyocyte apoptosis in the infarct border zone after I/R compared with wild-type littermates, indicating that endogenous GDF-15 limits myocardial tissue damage in vivo. Moreover, treatment with recombinant GDF-15 protected cultured cardiomyocytes from apoptosis during simulated I/R as shown by histone ELISA, TUNEL/Hoechst staining, and annexin V/propidium iodide fluorescence-activated cell sorting (FACS) analysis. Mechanistically, the prosurvival effects of GDF-15 in cultured cardiomyocytes were abolished by phosphoinositide 3-OH kinase inhibitors and adenoviral expression of dominant-negative Akt1 (K179M mutation). In conclusion, our study identifies induction of GDF-15 in the heart as a novel defense mechanism that protects from I/R injury.

Aged↗
PubMed2006

A double-blind, randomized, placebo-controlled multicenter clinical trial to evaluate the effects of the angiotensin II receptor blocker candesartan cilexetil on intimal hyperplasia after coronary stent implantation.

BACKGROUND: Preclinical data suggest beneficial effects of angiotensin II receptor blockers (ARBs) on neointima formation after vascular injury. Preliminary clinical data, however, revealed conflicting results. The AACHEN trial was a double-blind, randomized, placebo-controlled clinical multicenter trial to evaluate the effects of candesartan cilexetil on intimal hyperplasia after coronary stent implantation. METHODS: A total of 120 patients (61 +/- 9 years, 83% male) were randomized to receive either 32 mg candesartan cilexetil (active) or placebo starting 7 to 14 days before elective coronary stent implantation. A follow-up angiography including intravascular ultrasound assessment of the target lesion was performed 24 +/- 2 weeks after stent implantation. The primary end point was defined as the difference in neointimal area between groups as assessed by intravascular ultrasound. Secondary end points included differences in angiographic parameters (ie, restenosis rate) and incidence of major cardiac events. RESULTS: The mean stent length measured 15.0 +/- 4.9 mm in the active and 14.6 +/- 5.7 mm in the placebo group (P = .81). There was no significant difference in neointimal area between groups (2.1 +/- 1.0 vs 2.1 +/- 1.5 mm2, P = 1.00), nor were there differences in angiographic end point parameters. Major cardiac event rates were not significantly different between treatment groups (8% vs 11%, P = .75). CONCLUSIONS: High-dose candesartan cilexetil therapy in patients with symptomatic coronary artery disease undergoing coronary stent implantation does not reduce clinical event rates, restenosis rates, or neointimal proliferation after elective stent implantation.

Aged↗
PubMed2006

Bone-marrow-derived cell transfer after ST-elevation myocardial infarction: lessons from the BOOST trial.

Emerging evidence suggests that bone-marrow-derived stem and progenitor cells can be used to improve cardiac function after acute myocardial infarction. We tested this concept in the randomized, controlled, BOOST (bone marrow transfer to enhance ST-elevation infarct regeneration) clinical trial. Following successful percutaneous coronary intervention for acute ST-elevation myocardial infarction, patients received an intracoronary transfer of autologous bone marrow cells (BMCs). After 6 months, global left ventricular ejection fraction, as determined by magnetic resonance imaging, was significantly improved in the BMC-treated group compared with the control group. BMC transfer enhanced left ventricular systolic function, primarily in myocardial segments adjacent to the infarcted area, and also had a positive effect on diastolic function. BMC transfer did not increase the risk of adverse clinical events and did not promote in-stent re-stenosis or proarrhythmic effects. In principle, the effects of BMC transfer on ejection fraction were sustained at 18-month follow-up. Notably, radioactive labeling of BMCs and positron emission tomography showed that these beneficial effects are achieved with limited cardiac homing of BMCs after intracoronary application. Taken together, our studies indicate that intracoronary transfer of autologous BMCs is a safe, promising, and novel approach to further improving systolic function in patients with successful reperfusion after acute myocardial infarction.

Bone Marrow Cells↗
PubMed2006

Predictors of VT/VF-occurrence in ICD patients: results from the PROFIT-Study.

AIMS: Identification of risk factors for ventricular tachycardia/ventricular fibrillation (VT/VF) occurrence in patients with implantable cardioverter-defibrillators (ICD) is reasonable, because ICD patients with multiple risk factors might benefit from more aggressive anti-arrhythmic therapy for the prevention of arrhythmic events. Furthermore, in the era of prophylactic ICD therapy and limited healthcare resources, additional markers are needed for improved patient selection. METHODS AND RESULTS: Thus, in Prospective Analysis of Risk Factor for Appropriate ICD Therapy (PROFIT), we prospectively analyzed the role of ejection fraction (EF), N-terminal probrain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) class, atrial fibrillation, and QRS-duration as independent predictors for VT/VF occurrence in 250 ICD patients. Kaplan-Meier analysis showed that EF<40% (log-rank P=0.001), NT-proBNP levels higher than median (>or=405 ng/L; log-rank P=0.04), QRS-duration >or=150 ms (log-rank P=0.016), permanent atrial fibrillation (log-rank P=0.008), and higher NYHA class (log-rank P=0.029) were associated with VT/VF occurrence. By multivariate Cox regression analysis EF, QRS-duration and atrial fibrillation remained significantly associated with appropriate VT/VF therapy, whereas there was no relationship among NT-proBNP, NYHA class, and VT/VF occurrence. Stratifying patients according to the number of their independent risk factors (EF<40%, AF, QRS-width>or=150 ms) showed that patients with greater than or equal to two risk factors had a 100% 2-year risk of VT/VF occurrence, whereas patients with no or one risk factor had a 19.3 and 25% 2-year risk, respectively. CONCLUSIONS: EF<40%, permanent atrial fibrillation, and QRS>or=150 ms are independent predictors for VT/VF occurrence in predominantly secondary prophylactic ICD patients. Combining all independent predictors, we developed a risk score for VT/VF occurrence identifying a subgroup of patients with two or more risk factors who had a 100% 2-year risk. Future studies will reveal if this risk score helps to identify ICD patients suitable for empirical anti-arrhythmic therapy and to improve patient selection for prophylactic ICD therapy.

Aged↗