Drug-eluting stents for the treatment of pulmonary vein stenosis after atrial fibrillation ablation.

AIMS: Pulmonary vein (PV) stenosis (PVS) is a complication of radiofrequency PV isolation (PVI). Reported restenosis rates after balloon dilatation and bare-metal stent implantation are high. Drug-eluting stent implantation (DES) has not been reported in the setting of PVS. METHODS AND RESULTS: Patients suspected of having PVS after PVI based on clinical symptoms and transesophageal echocardiography (TEE) follow-up (FU) were referred for PV DES. One or more branches of the affected PV as documented by angiography were stented (paclitaxel or zotarolimus DES). Follow-up consisted of repeat PV angiography and TEE. Over a period of 2 years, five patients were treated with a total of eight DES. A paclitaxel DES was used in seven of eight implants. Mean FU was 12 ± 14 months during which all patients remained asymptomatic. Transesophageal echocardiography Doppler maximal flow velocity (V(max)) of the affected PVs rose from 58 ± 6 cm/s pre-PVI to 207 ± 20 cm/s pre-DES (+358%, P < 0.0001). After DES, V(max) decreased acutely with 86 ± 15 cm/s (-58%, P < 0.01). During FU, V(max) remained stable in three patients and increased moderately in one. Angiography at 3 months confirmed absence of restenosis in the first three patients and moderate (40%) restenosis in one patient. In one patient, an increase of V(max) back to pre-DES values correlated with a 65% peri-stent stenosis, treated with a redo DES. In total, after seven primary DES only one (asymptomatic) proximal margin restenosis required re-stenting. CONCLUSION: Initial experience with DES for PV stenosis suggests an excellent stent patency rate. Transesophageal echocardiography Doppler measurements provide a viable way of monitoring stent patency.

Slow wall motion rather than electrical conduction delay underlies mechanical dyssynchrony in postinfarction patients with narrow QRS complex.

INTRODUCTION: The mechanism of mechanical dyssynchrony in postinfarction patients with a narrow QRS complex is not defined but essential for cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Left ventricular electrical activation and subsequent wall motion were recorded for 16 patients with ischemic cardiomyopathy during intrinsic rhythm using a modified NOGA electromechanical mapping system. Ten patients presented mechanical dyssynchrony on tissue Doppler imaging, while 6 patients served as control subjects. The local activation time (LAT) was set by the maximum downslope of the unipolar electrogram. Local wall motion time (LMT) was defined as the time needed for the catheter tip to traverse half of its maximum inward deflection during systole. LAT and LMT were measured relative to the onset of the QRS complex. Electrical activation showed a septal-to-lateral pattern in all patients with a mean endocardial activation time of 65 +/- 13 ms. Control subjects exhibited 97.5% of all LMTs <290 +/- 17 ms. Delayed motion areas (cut-off LMT > 300 ms) showed no slowing of conduction. Wall motion time corrected for differences in electrical activation (LMT-LAT) was significantly longer in delayed (289 +/- 34 ms) than in regular (204 +/- 24 ms) motion areas (P = 0.002). Delayed motion segments were hypokinetic on echocardiography and presented a lower maximum inward motion (9.9 +/- 1.1 mm) compared to regular segments (10.9 +/- 1.2 mm) on electromechanical maps (P = 0.004). Viability, however, was preserved with unipolar and bipolar voltage amplitude >7 mV and >1.5 mV for 79% of all delayed motion areas. CONCLUSION: Dyssynchronous segments of an ischemic myocardium show unimpaired local activation but slow wall motion, thereby limiting the benefit of ventricular preexcitation via CRT.

Regional diastolic and systolic function by strain rate imaging for the detection of intramural viability during dobutamine stress echocardiography in a porcine model of myocardial infarction.

The aim of this study was to evaluate diastolic and systolic strain rate measurements for differentiation of transmural/nontransmural infarction during dobutamine stress echocardiography (DSE). An ameroid constrictor was placed around the circumflex artery in 23 pigs inducing chronic vessel occlusion. Five pigs without constrictor served as controls. During high-dose DSE systolic strain rates (SR(sys)), systolic and postsystolic strain values (epsilon(sys), epsilon(ps)) and early and late diastolic strain rates (SR(E) and SR(A)) were determined. At week 6, animals were evaluated regarding myocardial fibrosis. Histology revealed nontransmural in 14 and transmural infarction in 9 animals. In controls, dobutamine induced a linear increase of SR(sys) to 12.3 + or - 0.4 s(-1) at 40 microg/kg per minute (P = 0.001) and a linear decrease of SR(E) to -6.6 + or - 0.3 s(-1) (P = 0.001). In the nontransmural group, SR(sys), epsilon(sys), epsilon(ps) at rest, and during DSE were higher and SR(E) was lower than in the transmural infarction group (P = 0.01). Best predictors for viability were SR(sys) (ROC 0.96, P = 0.0003), SR(E) at 10 microg/kg per minute dobutamine stimulation (ROC 0.94, P = 0.001) and positive SR values during isovolumetric relaxation at 40 microg/kg per minute dobutamine (ROC 0.86, P = 0.004). The extension of fibrosis correlated with SR(sys) at rest, epsilon(sys) at rest, and SR(E) at rest (P < 0.001). For the detection of viability similar diagnostic accuracies of SR(E) and SRsys were seen (sensitivity 93%/93%, specificity 96%/94%, respectively). Diastolic SR analysis seems to be equipotent for the identification of viable myocardium in comparison to systolic SR parameters and allows the differentiation of nontransmural from transmural myocardial infarction with high diagnostic accuracy. (Echocardiography 2010;27:552-562).

Endocardial electrogram analysis after intramyocardial injection of mesenchymal stem cells in the chronic ischemic myocardium.

BACKGROUND: Cell injection therapies have been introduced for the treatment of patients with coronary heart disease. However, intramyocardial injection of bone marrow (BM)-derived cells may generate proarrhythmogenicity. METHODS: Two weeks after the placement of a circumflex artery-ameroid constrictor, 21 pigs received mesenchymal stem cells (MSC, n = 9), mononuclear (BM)-derived stem cells (MNC, n = 6), and placebo (n = 6) using a electromechanical mapping (EMM)-guided percutaneous transendocardial injection catheter. At week 6, EMM was repeated and the injected areas were analyzed in detail to evaluate local bipolar electrogram fragmentation, duration, and amplitude. Myocardial fibrosis was evaluated by a quantitative histological analysis. RESULTS: At week 6, the injection of MSC or MNC did not increase local electrogram fragmentation (MSC group: 1.4 +/- 0.3 vs. 1.3 +/- 0.2; MNC group: 1.4 +/- 0.2 vs. 1.3 +/- 0.2; P = NS), prolong electrogram duration (MSC group: 27.1 +/- 7.8 ms vs. 23.7 +/- 2.0 ms; MNC group: 27.8 +/- 3.5 ms vs. 26.8 +/- 5.6 ms; P = NS), or decrease bipolar voltages (MSC group 2.7 +/- 0.9 mV vs. 2.8 +/- 1.0 mV; MNC group 2.0 +/- 1.0 mV vs. 1.7 +/- 0.4 mV). From week 2 to week 6, mean left ventricular ejection fraction increased in the MSC group (37.9 +/- 4.2% vs. 45.9 +/- 2.2%; P = 0.039) only. Histological analysis of the ischemic regions revealed 17.6 +/- 5% myocardial fibrosis in the MNC group vs. 13.6 +/- 3.4% MSC vs. 28.7 +/- 8.7% in the control group (P = 0.038 and P = 0.013). No death occurred in any animal after the injection procedure. CONCLUSION: Intramyocardial injection of MSC or MNC do not increase fragmentation and duration of endocardial electrograms in the injected ischemic myocardium but attenuate ischemic damage and therefore may not create an electrophysiological substrate for reentry tachycardias.

[Percutaneous approaches for mitral valve interventions--a real alternative technique for standard cardiac surgery?]. / Die perkutane Mitralklappenintervention bei Mitralklappeninsuffizienz--eine Alternative zur konventionellen Herzchirurgie?

Standard therapy of advanced mitral valve regurgitation currently consists of mitral valve reconstruction through heart surgery including heart-lung machine employment. Typically, a ring is implanted and a leaflet reduced, if necessary, to approximate the posterior and anterior mitral valve leaflets to each other. Because of high comorbidity among this patient population, new and less burdening catheter-based techniques have been developed. Clinical etiology of mitral valve regurgitation is divided into two categories: "structural" versus "functional". The MONARC system of the Edwards Lifesciences company consists of three components--distal stent, bridge with bioabsorbing coating, proximal stent--and is implanted into the coronary sinus. The underlying principle is an indirect annuloplasty of the mitral valve annulus resulting from resorption of the bridge coating and leading to a reduction and indirect tightening of the mitral valve annulus. The EVOLUTION I (EV I) study in patients suffering from functional mitral regurgitation to a degree between 2+ and 4+ revealed--12 months after the MONARC implantation--a mitral valve regurgitation reduction from 2.48 to 1.78. The EV I study found interaction of the foreshortening bridge with the coronary arteries in some patients. This problem is most widely excluded by previous computed tomographic or angiographic examinations in the ongoing follow-up study EV II. Direct annuloplasty is made possible in case of functional mitral regurgitation by using the Mitralign Percutaneous Annuloplasty System (MPAS) of the Mitralign company. In doing so, an improved coadaptation of the mitral valve leaflet is achieved by inserting three sutures into the posterior mitral valve annulus and subsequent plicating.The MitraClip of the Evalve company uses the principle of the edge-to-edge technique. In doing so, the posterior and anterior leaflets are joined by implanting a clip, resulting in a reduction of mitral regurgitation with two diastolic orifices. In contrast to strukthe other two procedures, the MitraClip can be used for both functional and structural mitral valve regurgitation. The EVEREST I study and the EVEREST II study, as far as it has already been published, show that this procedure is secure and its results are very positive. The previous results of all three procedures show that catheter-based techniques for treating high-risk patients suffering from mitral valve regurgitation arrive at positive results in part, so that possibly a real alternative to conventional heart surgery will be available in the future.

Strain rate imaging for functional quantification of the left atrium: atrial deformation predicts the maintenance of sinus rhythm after catheter ablation of atrial fibrillation.

AIMS: The aim of the study was to investigate the atrial myocardial deformation properties using ultrasound strain rate (SR) imaging in patients after catheter ablation of atrial fibrillation (AF) and to compare its prognostic value in maintaining sinus rhythm. METHODS AND RESULTS: A total of 118 patients with AF (74 paroxysmal AF, 44 persistent AF) underwent transthoracic echocardiography with Doppler-derived SR examinations before and after ablation as well as during 3 months of follow-up (FU). Peak SR and strain (S) were measured at each left atrium (LA) segment (septal, lateral, anterior, inferior) during systole (LAs) and at early (LAe) and late diastole (LAa). Clinical and echocardiographic parameters of patients with maintained sinus rhythm during FU were compared with those with recurrent AF and controls (n = 25 patients). Of 118 patients 82 (69%) showed stable sinus rhythm during FU. Atrial myocardial properties after catheter ablation differed significantly in patients with paroxysmal AF (SR-LAs 2.5 s(-1), S-LAs 30%, SR-LAa -2.2 s(-1)) from patients with persistent AF (SR-LAs 2.3 s(-1), S-LAs 25%, SR-LAa -1.9 s(-1)) and controls (SR-LAs 4.1 s(-1), S-LAs 88%, SR-LAa -2.9 s(-1)) (P = 0.011). Best individual predictors of sinus rhythm maintenance were cut-off values of >2.25 s(-1) for septal and inferior SR-LAs and of >19.5% for inferior S-LAs (P < 0.001). LA deformation properties increased in patients with maintained sinus rhythm during FU in contrast to patients with recurrent AF (P = 0.001). CONCLUSION: SR imaging enables the quantitative assessment of the LA function and can be considered as a potential marker of atrial reverse remodelling. Patients with higher atrial S and SR after catheter ablation appear to have a greater likelihood of maintenance of sinus rhythm. This may have further implications for the anticoagulation regime and the risk of cardioembolic complications.

Intramyocardial transplantation of bone marrow-derived stem cells: ultrasonic strain rate imaging in a model of hibernating myocardium.

BACKGROUND: The aim of this study was to evaluate potential cardioprotective effects of bone marrow-derived stem cells in chronic ischemic myocardium regarding strain rate parameters during dobutamine stress echocardiography. METHODS: An ameroid constrictor was placed around the circumflex artery in 23 pigs to induce hibernating myocardium. Pigs received autologous mesenchymal stem cells (auto MSCs), allogeneic MSC (allo MSC), autologous mononuclear cells (auto MNCs), or placebo injections into the ischemic region. During dobutamine stress echocardiography, peak systolic strain rates (SR(sys)) and systolic and postsystolic strain values (epsilon(sys), epsilon(ps)) were determined. The animals were evaluated regarding myocardial fibrosis, neovascularization, apoptosis, and myocardial beta-adrenergic receptor density. RESULTS: The median ejection fraction was reduced in the control group compared with the auto MSC-, allo MSC-, and auto MNC-treated pigs (36.5% vs 46.0% vs 46.0% vs 41.5%; P = .001, respectively). Histopathology revealed a decreased myocardial fibrosis in auto MSC- (16.3%), allo MSC- (11.3%), and auto MNC- (16.7%) treated pigs compared with controls (31.0%; P = .004). The fibrosis and echocardiographic deformation data correlated in the posterior walls: rest peak SR(sys)r = -0.92; epsilon(sys)r = -0.86; 10 microg dobutamine stimulation peak SR(sys)r = -0.88, epsilon(sys), r = -0.87 (P = .0001). CONCLUSION: Endocardial injection of stem cells may induce cardioprotective effects in chronic ischemic myocardium and helps to keep the ischemic myocardium viable.

Transesophageal echocardiography: a follow-up tool after catheter ablation of atrial fibrillation and interventional therapy of pulmonary vein stenosis and occlusion.

BACKGROUND: Pulmonary vein stenosis (PVS) has been described as a complication after primary catheter ablation of atrial fibrillation (Afib). The purpose of this study was to evaluate the utility of transesophageal echocardiography (TEE) as follow-up tool after catheter ablation of Afib and interventional therapy of PVS and pulmonary vein occlusion (PVO). METHODS: We report on 28 patients with stenosis (PVS) of 33 pulmonary veins (PVs) and total PVO of 4 veins complicating ablation of Afib assessed by angiography and/or magnetic resonance imaging (MRI). Subsequently, transseptal PV angiograms were performed, followed by recanalization of three totally occluded PVs and balloon dilatation of seven severe PVS (in four cases combined with PV stenting). PVs were analyzed by multiplane TEE in an intraindividual comparison of preablation/preintervention and follow-up measurements of mean and peak flow velocity, velocity time integrals, and diameters. RESULTS: Of a total of 28 patients, 14 had mild PVS (n = 14), 9 had moderate PVS (n = 10), 6 had severe PVS (n = 8), and 4 patients showed totally occluded PVs (n = 4). In multivariate analysis flow velocities and vessel diameters showed significant differences (mild, moderate, and severe PVS and PVO; p = 0.001). Interventional benefits of balloon dilatation (n = 10) and stent implantation (n = 4), as well as in-stent restenosis could be detected (p = 0.014). In all recanalized vessels TEE showed reestablished flow. In occluded PVs no flow was detectable. The TEE vessel diameters correlated with angiography data (r = 0.87) and computed tomography/MRI (r = 0.90). CONCLUSIONS: TEE can be used as a follow-up tool after interventional therapy in patients after catheter ablation and acquired PVS/PVO. Restenosis/in-stent restenosis can be identified by analyzing the vessel diameters and blood flow characteristics.

Percutaneous endocardial injection of erythropoietin: assessment of cardioprotection by electromechanical mapping.

BACKGROUND: Apart from its well-known stimulation of erythropoiesis, erythropoietin (EPO) exhibits angiogenic and anti-apoptotic effects. These cellular protective effects have also been described in experimental acute myocardial infarction models. We investigated the effects of EPO in a porcine model of chronic progressive myocardial ischaemia. METHODS: At weeks 2 and 6 after implantation of a circumflex ameroid constrictor, endocardial electromechanical NOGA system (Biosense Webster, Inc., California, USA) mapping of the left ventricle, coronary and ventricular angiography, as well as echocardiography were performed. Two weeks after ameroid placement, 13 pigs were randomized with 7 pigs receiving 10.000 U EPO and 6 pigs receiving placebo into the ischaemic region using a NOGA guided percutaneous transendocardial injection catheter, MYOSTAR. After 6 weeks, histology (Masson's Trichrome) was analyzed. RESULTS: Endocardial electromechanical mapping showed an increase of mean unipolar voltage (UV) amplitude in the ischaemic myocardial segments in the EPO-treated animals (8.5 mV pre and 10.6 mV post treatment) and a significantly reduced ischaemic surface area compared to the control group (19% vs. 41%) suggesting a decline in ischaemic injury. Echocardiography revealed 2,2 hypokinetic segments of the lateral wall in the EPO group vs. 3,3 in the control groups. The mean ejection fraction was 64% in the EPO group and 55% in the placebo group. Quantitative histological analysis of the ischaemic regions revealed a reduction of myocardial fibrosis (8% vs. 28%) in the EPO group. CONCLUSION: Endocardial EPO injection may induce cardioprotective effects in hibernating myocardium and may attenuate the progression of ischaemic tissue damage.

Tissue velocity imaging during dobutamine stimulation for assessment of myocardial viability: segmental analysis in patients after myocardial infarction.

BACKGROUND: Dobutamine stress echocardiography (DSE) is an established method for the detection of viable myocardium, but evaluation of this method is subjective. Tissue velocity Imaging (TVI) allows quantitative analysis of regional myocardial wall motion by assessment of systolic myocardial velocities. The aim of this study was to evaluate the diagnostic value of DSE and TVI for detection of viable myocardium. METHODS: In 56 patients (58+/-12 years) with previous myocardial infarction (130+/-42 days, mean ejection fraction 42+/-15%) low-dose DSE was combined with analysis of peak systolic myocardial velocities (Vpeak) by TVI for assessment of myocardial viability. As reference served a follow-up echocardiography after successful revascularization (mean 91+/-3 days). RESULTS: Of a total of 896 segments 200 showed abnormal wall motion (31 mildly hypokinetic, 50 severely hypokinetic, 115 akinetic, 4 dyskinetic). In 125 of these 200 segments regional improvement of regional wall motion was observed (62.5% viable). An increase of Vpeak>1 cm/s during dobutamine stimulation allowed the identification of viable myocardium with a sensitivity of 82% and a specificity 82% (DSE: 77% and 80%). By receiver operating characteristic (ROC) curve analysis, a cut-off value of 1.0 cm/s was the best parameter to differ viable from nonviable myocardium (area under the curve 0.85; p<0.01; 95% CI 0.79 to 0.90). Improvement of global ejection fraction after revascularization (47+/-13%, p=0.11) corresponded with three TVI viable segments with a sensitivity of 92% and a specificity of 89% (p=0.012). CONCLUSIONS: TVI allows the identification of viable myocardium during dobutamine stimulation and enables a quantitative interpretation of DSE.

A difference ring theory for symbolic summation.

A summation framework is developed that enhances Karr's difference field approach. It covers not only indefinite nested sums and products in terms of transcendental extensions, but it can treat, e.g., nested products defined over roots of unity. The theory of the so-called [Formula: see text]-extensions is supplemented by algorithms that support the construction of such difference rings automatically and that assist in the task to tackle symbolic summation problems. Algorithms are presented that solve parameterized telescoping equations, and more generally parameterized first-order difference equations, in the given difference ring. As a consequence, one obtains algorithms for the summation paradigms of telescoping and Zeilberger's creative telescoping. With this difference ring theory one gets a rigorous summation machinery that has been applied to numerous challenging problems coming, e.g., from combinatorics and particle physics.

Electromechanical mapping for determination of myocardial contractility and viability. A comparison with echocardiography, myocardial single-photon emission computed tomography, and positron emission tomography.

OBJECTIVE: The purpose of this study was to validate electromechanical viability parameters with combined myocardial perfusion and metabolic imaging and echocardiography. BACKGROUND: The NOGA System is a catheter-based, non-fluoroscopic, three-dimensional endocardial mapping system. This unique technique allows accurate simultaneous assessment of both local electrical activity and regional contractility. METHODS: The results of NOGA, myocardial single-photon emission computed tomography (SPECT), positron emission tomography, and echocardiography in 51 patients with coronary artery disease and a pathologic SPECT study were transcribed in a nine-segment bull's-eye projection and compared. The local shortening of normally contracting segments, as shown by echocardiography, was 9.2 +/- 5.1%, which decreased to 6.6 +/- 5.0% and 4.1 +/- 5.2% in hypokinetic and akinetic segments. The highest unipolar voltage (11.2 +/- 5.0 mV) and local shortening (8.2 +/- 5.0%) characterized normally perfused segments. Fixed perfusion defects with normal or limited 18-fluoro-2-deoxy-D-glucose uptake indicating viability had a significantly higher unipolar voltage than did scar tissue (7.25 +/- 2.7 vs. 5.0 +/- 3.1 mV, p = 0.029). CONCLUSION: Electromechanical parameters sufficiently defined the viability state of the myocardium and showed good concordance with the findings by nuclear perfusion and metabolism imaging and echocardiography. The NOGA technique provides all the relevant information immediately after coronary angiography and enables the physician to proceed with therapy in the same setting.

Downsizing of the mitral valve and coronary revascularization in severe ischemic mitral regurgitation results in reverse left ventricular and left atrial remodeling.

OBJECTIVE: Data of combined mitral downsizing by restrictive prosthetic ring annuloplasty and coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy and moderately severe to severe mitral regurgitation (MR) are rare, and little is known about the effect on reverse left ventricular (LV) and left atrial (LA) remodeling. METHODS: Thirty-eight patients (70.6+/-8.3 years) with coronary artery disease, ischemic cardiomyopathy (LV ejection fraction [LVEF] 31+/-8%) and moderately severe to severe MR (grade 3.6+/-0.5) underwent CABG and mitral downsizing by 2-4 ring sizes. Clinical follow-up and serial transthoracic echocardiographic studies were performed after surgery (discharge, 3+/-0.5 months, 13+/-7 months) to assess survival, NYHA class, MR, leaflet coaptation height, LA and LV dimensions/volumes, fractional shortening (FS) and LVEF. RESULTS: Early mortality (<30 days) was 2.6%, survival at follow-up was 92 and 85%, respectively. NYHA class improved from 3.3+/-0.6 to 1.5+/-0.6 (P<0.001). Residual MR at discharge and at follow-up was grade 0.5 and 0.6, respectively (P<0.001). Leaflet coaptation height was 8+/-1 mm and did not change over time. LV end-diastolic, end-systolic and LA dimensions decreased from 60+/-7 to 57+/-8 mm, from 47+/-9 to 42+/-9 mm and from 51+/-5 to 45+/-4 mm, FS increased from 23+/-9 to 28+/-10% (P<0.001); LV end-diastolic and end-systolic volumes decreased from 188+/-33 to 171+/-30 ml and from 129+/-35 to 105+/-33 ml, LVEF increased from 31+/-8 to 39+/-10% (P<0.001). CONCLUSIONS: Combined mitral downsizing and CABG surgery was performed with excellent clinical results: only minimal residual MR, a significant reduction of LA dimension and an increase of LV contractility due to reverse remodeling were observed.

Percutaneous, transendocardial injection of bone marrow-derived mononuclear cells in heart failure patients following acute ST-elevation myocardial infarction: ALSTER-Stem Cell trial.

AIMS: Patients with symptomatic heart failure following acute ST-elevation myocardial infarction (STEMI) received transendocardial application of bone marrow-derived mononuclear cells (BMC) to improve left ventricular (LV) function and clinical outcome. METHODS AND RESULTS: Patients (n=12) with LV ejection fraction (EF) <45% and NYHA Class ≥II received NOGA-guided transendocardial injection of BMC into the infarction border zone 17.5±0.8 days following successful interventional revascularisation after STEMI. A matched control group (n=11) was generated from the source data of the previously published LIPSIAbciximab-STEMI trial. Primary and secondary endpoints were derived from comparisons of baseline vs. six-month follow-up cardiac magnetic resonance imaging (CMR) measurements and clinical assessments. Following cell therapy we observed a significant increase of EF (+7.9±1.5%, p=0.001) while the control group showed no change. This effect was driven by a reduction of LV end-systolic volume (ESV) by -27.5±6.5 ml (p=0.001); LV end-diastolic volume (EDV) and scar volu-me remained unchanged. A significant decrease of NYHA Class was found only in the cell therapy group (-0.75 vs. -0.18, p=0.04). Findings were also translated into enhancement of clinical assessments (rehospitalisation for decompensated heart failure, six-minute walk test, NT-proBNP levels). CONCLUSION: The data suggest transendocardial injection of BMC can be used safely in patients with sympto-matic heart failure following acute STEMI. These prospective, preliminary data of a well-characterised, small cohort suggest efficiency compared to routine treatment.

Unfair permutations.

We study unfair permutations, which are generated by letting [Formula: see text] players draw numbers and assuming that player [Formula: see text] draws [Formula: see text] times from the unit interval and records her largest value. This model is natural in the context of partitions: the score of the [Formula: see text]th player corresponds to the multiplicity of the summand [Formula: see text] in a random partition, with the roles of minimum and maximum interchanged. We study the distribution of several parameters, namely the position of player [Formula: see text], the number of inversions, and the number of ascents. To perform some of the heavy computations, we use the computer algebra package Sigma.

Potential and clinical utility of stem cells in cardiovascular disease.

The recent identification of bone marrow-derived adult stem cells and other types of stem cells that could improve heart function after transplantation have raised high expectations. The basic mechanisms have been studied mostly in murine models. However, these experiments revealed controversial results on transdifferentiation vs transfusion of adult stem cells vs paracrine effects of these cells, which is still being debated. Moreover, the reproducibility of these results in precisely translated large animal models is still less well investigated. Despite these weaknesses results of several clinical trials including several hundreds of patients with ischemic heart disease have been published. However, there are no solid data showing that any of these approaches can regenerate human myocardium. Even the effectiveness of cell therapy in these approaches is doubtful. In future we need in this important field of regenerative medicine: i) more experimental data in large animals that are closer to the anatomy and physiology of humans, including data on dose effects, comparison of different cell types and different delivery routes; ii) a better understanding of the molecular mechanisms involved in the fate of transplanted cells; iii) more intensive research on genuine regenerative medicine, applying genetic regulation and cell engineering.

Stem cell therapy in cardiovascular disorders.

Heart insufficiency remains the leading cause of death despite pharmacological and interventional therapy as well as primary and secondary prevention. Laboratory research on cardiac repair implementing stem cells and progenitor cells has raised great expectations as well as controversies. The potential of diverse progenitor cells to repair damaged heart tissue includes replacement (tissue transplant), restoration (activation of resident cardiac progenitor cells, paracrine effects), and regeneration (stem cell engraftment forming new myocytes). Based on promising experimental results clinical trials including several hundreds of patients with ischemic heart disease have been initiated using mostly bone marrow-derived cells. Probably, due to a lack of standardization of cell isolation and delivery methods these trials showed controverse results regarding effectiveness. However, significant therapeutic regeneration of human myocardium could not be proven until now. Several issues are at debate concerning the translation of the experimental data into the clinic discussing the adequate cell type, dosing, timing, and delivery mode of myocardial stem cell therapy. This review focuses on the potential and clinical translation of cell based therapies in cardiovascular disease.