Coronary intravascular lithotripsy and rotational atherectomy for severely calcified stenosis: Results from the ROTA.shock trial.

BACKGROUND: Severely calcified coronary lesions present a particular challenge for percutaneous coronary intervention. AIMS: The aim of this randomized study was to determine whether coronary intravascular lithotripsy (IVL) is non-inferior to rotational atherectomy (RA) regarding minimal stent area (MSA). METHODS: The randomized, prospective non-inferiority ROTA.shock trial enrolled 70 patients between July 2019 and November 2021. Patients were randomly (1:1) assigned to undergo either IVL or RA before percutaneous coronary intervention of severely calcified coronary lesions. Optical coherence tomography was performed at the end of the procedure for primary endpoint analysis. RESULTS: The primary endpoint MSA was lower but non-inferior after IVL (mean: 6.10 mm2 , 95% confidence interval [95% CI]: 5.32-6.87 mm2 ) versus RA (6.60 mm2 , 95% CI: 5.66-7.54 mm2 ; difference in MSA: -0.50 mm2 , 95% CI: -1.52-0.52 mm2 ; non-inferiority margin: -1.60 mm2 ). Stent expansion was similar (RA: 0.83 ± 0.10 vs. IVL: 0.82 ± 0.11; p = 0.79). There were no significant differences regarding contrast media consumption (RA: 183.1 ± 68.8 vs. IVL: 163.3 ± 55.0 mL; p = 0.47), radiation dose (RA: 7269 ± 11288 vs. IVL: 5010 ± 4140 cGy cm2 ; p = 0.68), and procedure time (RA: 79.5 ± 34.5 vs. IVL: 66.0 ± 19.4 min; p = 0.18). CONCLUSION: IVL is non-inferior regarding MSA and results in a similar stent expansion in a random comparison with RA. Procedure time, contrast volume, and dose-area product do not differ significantly.

Everolimus- vs. novolimus-eluting bioresorbable scaffolds in patients with acute coronary syndrome.

BACKGROUND: Limited data exist on bioresorbable scaffolds (BRS) in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate novolimus-eluting BRS (DESolve) as interventional treatment for patients with ACS, and to compare its 12-month outcomes with the everolimus-eluting bioresorbable scaffolds (Absorb). METHODS: In this retrospective study, patients with ACS (including unstable angina pectoris, ST-segment elevation myocardial infarction, or non-ST-segment elevation myocardial infarction) treated with either the Absorb or the DESolve BRS were evaluated in a 1:1 matched-pair analysis. Major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization, were evaluated as a major endpoint. The occurrence of scaffold thrombosis was also assessed. RESULTS: A total of 102 patients were eligible for this analysis. The rate of MACE at 12 months was comparable between the Absorb and the DESolve group (8.3% vs. 6.8%, p = 0.738). The occurrence of target lesion revascularization (6.2% vs. 4.7%; p = 0.700) and scaffold thrombosis (4.1% vs. 2.1%; p = 0.580) was comparable as well. All instances of scaffold thrombosis occurred within 30 days of the index procedure. CONCLUSION: In this study, similar 12-month event rates were observed for both BRS types after implantation for the treatment of ACS.

[Heart valve disesases : How sufficient is the knowledge of the German population?] / Herzklappenerkrankungen : Wie aufgeklärt ist die deutsche Bevölkerung?

To evaluate the awareness and knowledge of the German population regarding diseases in general, a survey of 1446 people aged 60 years or older was conducted in 14 German towns. The focus was on heart valve diseases with special emphasis on aortic valve stenosis (AS). While cancer was the disease that respondents were most concerned about (25.2%), only 3.3% were concerned about heart valve diseases. In this respect, the knowledge was broadly limited: only 7.4% of participants claimed to have some familiarity with heart valve diseases and only 12.5% could correctly describe the symptoms of AS. Even so, 35.0% of the participants could correctly name the number of human heart valves, 71.6% knew at least one therapy option for AS and 30.6% were familiar with transcatheter aortic valve implantation (TAVI). After providing a brief clarification of the prevalence, symptoms and course of AS, 45.6% of respondents were more concerned about the condition, 15.7% wanted to know more about the symptoms of AS and 4.7% even recognized the typical symptoms in themselves. Most of the participants would like to seek more information preferably in discussion with a specialist physician (77.2%), with their general practitioner (43.2%) or using the internet (29.7%). Despite its high prevalence, high morbidity and mortality, the vast majority of the German population were neither concerned nor fully aware of treatment options for AS. There is a strong case for public awareness campaigns that provide better knowledge of AS, and support check-ups that enable timely treatment and the avoidance of unnecessary hospitalization and death.

The contribution of comorbidities to mortality in hospitalized patients with heart failure.

BACKGROUND: Heart failure (HF) with reduced ejection fraction (HFrEF) has a worse prognosis than HF with preserved EF (HFpEF). The study aimed to evaluate whether different comorbidity profiles of HFrEF- and HFpEF-patients or HF-specific mechanisms contribute to a greater extent to this difference. METHODS: We linked data from two health insurances to data from a cardiology clinic hospital information system. Patients with a hospitalization with HF in 2005-2011, categorized as HFrEF (EF < 45%) or HFpEF (EF ≥ 45%), were propensity score (PS) matched to controls without HF on comorbidites and medication to assure similar comorbidity profiles of patients and their respective controls. The balance of the covariates in patients and controls was compared via the standardized difference (SDiff). Age-standardized 1-year mortality rates (MR) with 95% confidence intervals (CI) were calculated. RESULTS: 777 HFrEF-patients (1135 HFpEF-patients) were PS-matched to 3446 (4832) controls. Balance between patients and controls was largely achieved with a SDiff < 0.1 on most variables considered. The age-standardized 1-year MRs per 1000 persons in HFrEF-patients and controls were 267.8 (95% CI 175.9-359.8) and 86.1 (95% CI 70.0-102.3). MRs in HFpEF-patients and controls were 166.2 (95% CI 101.5-230.9) and 61.5 (95% CI 52.9-70.1). Thus, differences in MRs between patients and their controls were higher for HFrEF (181.7) than for HFpEF (104.7). CONCLUSIONS: Given the similar comorbidity profiles between HF-patients and controls, the higher difference in mortality rates between HFrEF-patients and controls points more to HF-specific mechanisms for these patients, whereas for HFpEF-patients a higher contribution of comorbidity is suggested by our results.

Intracoronary pressure measurement differences between anterior and posterior coronary territories.

INTRODUCTION: Intracoronary pressure measurements have improved assessment of angiographic intermediate coronary stenoses. Methodically, pressure equalization and actual measurements are frequently performed at different height levels, depending on the particular coronary territory analyzed. Considering a hypothetical influence of hydrostatic pressure and the supine position of the patient, differences in the results of intracoronary measurements between anterior and posterior vessels seem likely. The purpose of this study was to compare the results of intracoronary pressure measurements between anterior and posterior coronary territories. METHODS: Intracoronary pressure measurements of 214 coronary stenoses in 158 patients were analyzed. Fractional flow reserve (FFR) was measured in all stenosis and instantaneous wave-free ratio (iFR) in 197 stenoses in 144 patients. RESULTS: Both FFR (0.79 vs. 0.87, p < 0.001) and iFR values (0.86 vs. 0.94, p < 0.001) were significantly higher in posterior compared to anterior coronary vessels. Patients with only anterior or posterior lesions did not differ regarding clinical or lesion characteristics, in particular coronary stenosis severity (62.5 vs. 61.6 %, p = 0.27). CONCLUSIONS: Results of intracoronary measurements were systematically higher in the posterior coronary vessels when compared with anterior vessels. This phenomenon was independent of coronary stenosis severity or any clinical characteristics in our study population.

Temporal trends in transcatheter and surgical aortic valve replacement : An analysis of aortic valve replacements in Germany during 2012-2014.

This analysis of the data of the obligatory quality assurance programme AQUA shows the perioperative risk as well as the procedural outcome evaluated by the observed versus expected in-hospital mortality ratio (O/E ratio) of 62,872 patients undergoing isolated surgical (sAVR), transcatheter transvascular (TV-), or transapical (TA-) aortic valve replacement (TAVI) from 2012 to 2014 in Germany. The number of TAVI procedures increased from 9,352 in 2012 to 13,278 in 2014, whereas the number of sAVR remained constant (2012: 9,949; 2014: 9,953). Between 2012 and 2014, the number of TAVI implanted in patients with a logistic EuroScore I (logESI) of ≤10 % (2012: 21 %; 2014: 26 %) as well as with a logESI <20 % (2012: 57 %; 2014: 64 %) increased. In-hospital mortality in TAVI patients decreased from 5.2 % (TV: 5.0 %; TA: 7.4 %) in 2012 to 4.2 % (TV: 3.8 %; TA: 5.5 %) in 2014, whereas it was stable for sAVR patients (2012: 2.8 %; 2014: 2.6 %). The O/E ratio of TAVI patients decreased from 0.91 (TV: 0.79; TA: 1.2) to 0.73 (TV: 0.69; TA: 0.89), whereas this ratio remained constant for sAVR patients (2012: 0.92; 2014: 0.93). In summary, estimated surgical risk, in-hospital mortality, as well as the O/E ratio for patients undergoing TAVI declined constantly during the last 3 years.

[Bifurcation lesions : How should they be assessed and treated?] / Bifurkationsläsionen : Wie beurteilen ­ wie vorgehen?

Bifurcation lesions are a therapeutic challenge in the interventional treatment of coronary artery disease. Thus, consideration of anatomical aspects and selection of the most appropriate strategy for an individual bifurcation have an impact on the interventional outcome. Accordingly, assessment of the type of bifurcation stenosis, including the relevance of the side branches, vessel diameter and the angle between the two branches are critical for the optimal choice of interventional strategy. The fractional flow reserve (FFR) is a parameter that provides a measure of the severity of coronary stenosis and despite some limitations, FFR can be applied to bifurcation lesions. In addition, intravascular imaging tools, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can be used to determine anatomical configurations.

[Linkage of statutory health insurance data with those of a hospital information system: feasible, but also "useful"?]. / Verknüpfung von Routinedaten der Gesetzlichen Krankenversicherung mit Daten eines Krankenhausinformationssystems: Machbar, aber auch "nützlich"?

AIM: Administrative data are increasingly being linked with other data sources for research purposes in the field of epidemiology and health services research abroad. In Germany, the direct linkage of routine data of statutory health insurance (SHI) providers with other data sources is complicated due to strict data protection requirements. The aim of this analysis was to evaluate an indirect linkage of SHI routine data with data of a hospital information system (HIS). METHODS: The dataset comprised data from 2004 to 2010 from 2 sickness funds and one HIS. In both data sources, hospitalisations were restricted to admissions into one hospital with at least one diagnosis of heart failure. The 2 data sources were linked, in cases of the agreement of the admission and discharge dates, as well as the agreement of at least a certain percentage of diagnoses in HIS data when compared to SHI data (full coding depth). Based on the direct linkage using the pseudonymised insurance number as gold standard, the proposed linkage approach was evaluated by means of test statistics. Furthermore, the completeness of relevant information of the HIS was described. RESULTS: The dataset contained 3 731 hospitalisations from the HIS and 8 172 hospitalisations from the SHI routine data. The sensitivity of the linkage approach was 86.7% in the case of an agreement of at least 30% of the diagnoses and decreased to 41.7% in the case of 100% agreement in the diagnoses. The specificity was almost 100% at all studied cut-offs of agreement. Anthropometric measures and diagnostic information were available only for a small fraction of cases in the data of the HIS, whereas information on the health status and on laboratory information was comparatively complete. CONCLUSION: For the linkage of SHI routine data with complementary data sources, indirect linkage methods can be a valuable alternative in comparison to direct linkage, which is time-consuming with regard to planning and application. Since the proposed approach was used in a relatively small sample and a restricted patient population, a replication using nation-wide data without respective restrictions would require an extension of the algorithm. Furthermore, the large administrative effort seems questionable considering the comparatively high amount of missing values in interesting information in the HIS.

[Physical characterization of decellularized cartilage matrix for reconstructive rhinosurgery]. / Physikalische Charakterisierung dezellularisierter Knorpelmatrix zur Anwendung in der Rhinochirurgie.

BACKGROUND: The use of autologous auricular and rib cartilage for the reconstruction of nasal defects and deformities is associated with a number of disadvantages. The development of alternative materials is therefore the focus of intensive research. Recent studies demonstrated that decellularized cartilage is a promising material for cartilage tissue engineering. Hence, the aim of this study was to characterize the materials surface and cellular reactions to the decellularized cartilage matrix in long term-3D-culture. MATERIAL AND METHODS: Material geometry of decellularized cartilage was examined by microcomputed tomography as well as material characteristics by scanning and transmission electron microscopy. The expression of integrins on the surface of human chondrocytes was determined after seeding and migration into the scaffold. RESULTS: After decellularization an obvious enlargement of the matrix surface and an intensive interaction between the chondrocytes and the collagen matrix was observed. ITGA1 and ITGB1 were upregulated indicating chondrogenic differentiation. CONCLUSION: Therefore, decellularized porcine cartilage provides an optimal microstructure for human chondrocytes with respect to cell integration and matrix production. Thus, it offers promising characteristics for clinical application in reconstructive surgery.

Coupled variable selection for regression modeling of complex treatment patterns in a clinical cancer registry.

For determining a manageable set of covariates potentially influential with respect to a time-to-event endpoint, Cox proportional hazards models can be combined with variable selection techniques, such as stepwise forward selection or backward elimination based on p-values, or regularized regression techniques such as component-wise boosting. Cox regression models have also been adapted for dealing with more complex event patterns, for example, for competing risks settings with separate, cause-specific hazard models for each event type, or for determining the prognostic effect pattern of a variable over different landmark times, with one conditional survival model for each landmark. Motivated by a clinical cancer registry application, where complex event patterns have to be dealt with and variable selection is needed at the same time, we propose a general approach for linking variable selection between several Cox models. Specifically, we combine score statistics for each covariate across models by Fisher's method as a basis for variable selection. This principle is implemented for a stepwise forward selection approach as well as for a regularized regression technique. In an application to data from hepatocellular carcinoma patients, the coupled stepwise approach is seen to facilitate joint interpretation of the different cause-specific Cox models. In conditional survival models at landmark times, which address updates of prediction as time progresses and both treatment and other potential explanatory variables may change, the coupled regularized regression approach identifies potentially important, stably selected covariates together with their effect time pattern, despite having only a small number of events. These results highlight the promise of the proposed approach for coupling variable selection between Cox models, which is particularly relevant for modeling for clinical cancer registries with their complex event patterns.

[Dietary supplements and cardiovascular diseases]. / Nahrungsmittelergänzung in der Prävention kardiovaskulärer Erkrankungen: Keine Empfehlung ohne Wirksamkeitsbeleg.

Dietary supplements and so-called "functional foods" are advertised for primary and secondary prevention of cardiovascular diseases. However, there are no studies available that show that these products reduce "hard cardiovascular outcomes" such as myocardial infarction or stroke. Moreover, some studies have shown that dietary supplementation might do more harm than good. Therefore, prior to a general recommendation more data on safety and effectiveness are necessary.

[BNP elevation due to a subdural hematoma - misled by a biomarker]. / BNP-Erhöhung bei subduralem Hämatom - durch einen Biomarker in die Irre geführt.

HISTORY AND ADMISSION FINDINGS: A 73-year-old man with a mechanical aortic valve and a history of congestive heart failure was admitted to our hospital with an unspecifically reduced general condition. Physical examination was normal according to age apart from mechanic valve closure tones and a 2/6 sytolic murmur at Erb's point. INVESTIGATIONS: Inflammation markers were elevated (leukocytosis 22 100/µl, CRP 22 mg/dl ), there was mild anemia (hemoglobin 9.7 mg/dl) and digitoxin blood level was increased to 56 µg/l (therapeutic range 10-30 µg/l). Because NT-proBNP was highly elevated, further diagnostics focused on cardiac causes of BNP elevation despite missing clinical symptoms. Transesophageal echocardiography was inconspicuous and blood cultures were negative. Therefore an infection of unknown origin or an emerging endocarditis were presumed. TREATMENT AND COURSE: Pragmatic treatment with antibiotics and diuretics as well as discontinuation of digitoxin led to normalization of leukocytes, CRP and digitoxin levels. But the patient's general condition deteriorated further, NT-proBNP rose to 37731 pg/ml and the patient became disoriented. On thorough questioning the patient's relatives stated that he had fallen 6 weeks previously. Computed tomography then revealed a large chronic subdural hematoma which had caused the NT-proBNP elevation. The patient was operated successful. CONCLUSION: In patients with elevated BNP and atypical symptoms neurological causes should be considered.

[Pulsatile tumor on the left side of the thorax after heart surgery]. / Pulsierender Tumor auf der linken Thoraxseite nach Herzoperation.

HISTORY AND ADMISSION FINDINGS: In a 67-year-old woman a large haematoma developed on the left side of the chest after two sternotomies because of an aortic valve and aorta ascendens replacement for aortic type A dissection. After a few weeks, a pulsating mass remained over the 6th left parasternal intercostal space. A consultant general surgeon punctured the lesion and aspirated bright red blood. The patient was transferred for further diagnostic procedures to the cardiology department. INVESTIGATIONS: Ultrasound examination of the pulsating mass showed a 35 mm echo-free cavity with turbulent flow in the color Doppler. To clarify the inflow into this perfused cavity magnetic resonance imaging (MRI) with angiography of the thorax vessels was performed. The cavity was found to be a perfused pseudoaneurysm originating from the native left mammary artery. The aneurysm had a 6 mm long neck and a diameter of 35 mm. An interventional closure was planned. TREATMENT AND COURSE: With access via the right groin a 6 French LIMA guiding catheter was inserted into the origin of the left internal mammary artery. With a 0.014 inch Balance Middleweight coronary guide wire it was possible to engage the pseudoaneurysm. Over the wire, a tracker 18 infusion catheter was pushed down and placed in the pseudoaneurysm. The closure was performed by insertion of a 0.018 inch 3 cm/4 mm Hilal Microcoil into the aneurysm neck. The mammary artery was anatomically and functionally unaffected. After the deposit of a coil, the inflow was stopped. An ultrasound showed a blood coagulation in the pseudoaneurysm, which decreased in size over time. CONCLUSION: After sternotomy a pseudoaneurysm of the left internal mammary artery had developed. As a noninvasive imaging modalitiy the magnetic resonance angiography showed well the exact flow into the aneurysm and allowed the planning of the intervention. The closure was achieved with a microcoil with preservation of the native internal mammary artery.

Stem cell-mediated natural tissue engineering.

Recently, we demonstrated that a fully differentiated tissue developed on a ventricular septal occluder that had been implanted due to infarct-related septum rupture. We suggested that this tissue originated from circulating stem cells. The aim of the present study was to evaluate this hypothesis and to investigate the physiological differentiation and transdifferentiation potential of circulating stem cells. We developed an animal model in which a freely floating membrane was inserted into each the left ventricle and the descending aorta. Membranes were removed after pre-specified intervals of 3 days, and 2, 6 and 12 weeks; the newly developed tissue was evaluated using quantitative RT-PCR, immunohistochemistry and in situ hybridization. The contribution of stem cells was directly evaluated in another group of animals that were by treated with granulocyte macrophage colony-stimulating factor (GM-CSF) early after implantation. We demonstrated the time-dependent generation of a fully differentiated tissue composed of fibroblasts, myofibroblasts, smooth muscle cells, endothelial cells and new blood vessels. Cells differentiated into early cardiomyocytes on membranes implanted in the left ventricles but not on those implanted in the aortas. Stem cell mobilization with GM-CSF led to more rapid tissue growth and differentiation. The GM-CSF effect on cell proliferation outlasted the treat ment period by several weeks. Circulating stem cells contributed to the development of a fully differentiated tissue on membranes placed within the left ventricle or descending aorta under physiological conditions. Early cardiomyocyte generation was identified only on membranes positioned within the left ventricle.

Clinical outcome of patients treated with an early invasive strategy after out-of-hospital cardiac arrest.

Little is known about the impact of early invasive treatment in patients following out-of-hospital cardiac arrest (OHCA). The present study investigated the clinical characteristics and long-term prognosis of 1254 patients with suspected acute coronary syndrome, including 65 with OHCA who underwent successful cardiopulmonary resuscitation (CPR) and 1189 patients who did not require CRP. All patients underwent immediate coronary angiography even if clear signs of myocardial infarction (MI) were absent. The incidence of ST-elevation and non-ST-elevation MI did not differ between the two groups. Cardiac biomarkers were significantly higher in CPR patients despite a shorter period from symptom onset to admission. The 6-month mortality rate was 29% in the CPR group and 4% in the non-CPR group, with > 90% of fatalities occurring ≤ 3 weeks after admission. In summary, early invasive treatment leads to a considerably reduced mortality and improved prognosis in patients after OHCA.

Calcium-dependent signalling is essential during collateral growth in the pig hind limb-ischemia model.

We investigated the effect of pharmacological activation of the Ca(2+)-channel transient receptor potential cation channel, subfamily V, member 4 (TRPV4) on collateral growth in a pig hind limb-ischemia model thereby identifying subcellular mechanisms. Domestic pigs received femoral artery ligature and were randomly assigned to one of the following groups (each n=6): (1) 4alpha-phorbol 12,13-didecanoate (4alphaPDD) treatment; (2) treatment with an arterio-venous shunt (AV-shunt) distal to the occlusion; or (3) implantation of NaCl-filled minipump. Six sham-operated pigs acted as controls. Aortic and peripheral mean arterial pressure (MAP) measurements were performed to assess the collateral flow index (CFI). Tissue was isolated from M. quadriceps for immunohistochemistry and from isolated collateral arteries for quantitative real time PCR (qRT-PCR). Shortly after ligature the CFI dropped from 0.96+/-0.02 to 0.21+/-0.02 in all ligature-treated groups. In ligature-only-treated pigs CFI increased to 0.56+/-0.03 after 7days. Treatment with 4alphaPDD led to an enhancement of CFI compared with ligature alone (0.73+/-0.03). CD31-staining showed improved arteriolar density. Increased Ki67 staining in collaterals indicated proliferation. qRT-PCR and Western blot analysis showed upregulation or modulation of Ca(2+)-dependent transcription factors nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), Kv channel interacting protein 3, calsenilin (KCNIP3/CSEN/DREAM), and myocyte enhancer factor 2C (MEF2C) in 4alphaPDD- and AV-shunt-treated pigs compared with controls. Improved CFI after 4alphaPDD treatment identifies TRPV4 as an initial fluid shear-stress sensor and collateral remodelling and growth trigger. Subcellularly, modulation of Ca(2+)-dependent transcription factors indicates a pivotal role for Ca(2+)-signalling during arteriogenesis.

[Historical and current pathophysiological concepts of stress (Tako-Tsubo) cardiomyopathy]. / Historische und gegenwärtige pathophysiologische Konzepte der Tako-Tsubo-Kardiomyopathie.

Tako-Tsubo cardiomyopathy (TTC), also referred to as stress cardiomyopathy (SCM), was first described in the 1990s and is characterized by transient left ventricular dysfunction. Its incidence represents 1-2% of all acute coronary syndromes (ACS). In most cases extreme emotional or physical stress precedes this syndrome. The majority of patients affected are postmenopausal women. Since its first description, various hypotheses regarding the pathophysiology of TTC have been discussed. From a historical perspective, coronary vasospasm has often been proposed as a possible cause of this disorder. However, reviews from numerous registries were able to demonstrate that coronary vasospasm plays only a minor role in the pathogenesis of TTC. Several groups showed disturbances in myocardial microcirculation and energy metabolism in the acute phase of TTC. Nevertheless, with regard to the data currently available, it cannot be differentiated whether these changes are the cause or rather the result of TTC. However, recent concepts include an excessive catecholamine overload and morphological changes which are unequivocally documented in TTC. The relation between elevated catecholamine levels and myocardial dysfunction analogous to TTC could be confirmed in animal experiments.In summary, it can be assumed that TTC is caused by an excessive cardiotoxic release of catecholamines. Ventricular dysfunction can be explained by increased numbers of ß-adrenergic receptors in the apex, leading to greater vulnerability to catecholamine overload. Individual anatomical differences in the sympathoadrenergic system and distribution from ß-adrenergic receptors are presumably responsible for the interindividual occurrence of wall motion abnormalities in TTC.

Desynchronization: a novel model to induce heart failure.

BACKGROUND: Previous large animal heart failure models led to inhomogeneous results. Therefore, we developed a novel model combining rapid pacing with forced ventricular desynchronization. METHODS: Heart failure was induced in 20 pigs during a pacing period of 21 days. Group A (n = 10) received one right ventricular lead (220 bpm). In group B (n = 10), two leads were implanted in different right ventricular regions with beat-to-beat alternation of activation sites (each lead 110 bpm). Sham-operated pigs (n = 6) served as controls. Hemodynamics were invasively evaluated and tissue was analyzed by immunohistochemistry and zymography. RESULTS: Hemodynamics were significantly more impaired in group B with an increase of pulmonary capillary wedge and central venous pressure and a reduction of cardiac index (control 4.3 +/- 0.1 l/min/m (2); A 3.6 +/- 0.2; B 2.9 +/- 0.2, P < 0.05). Heart-to-body weight ratio was significantly higher in group B. Histological analyses showed a significant increase of cell diameters and interstitial fibrosis with significantly higher collagen contents in group B. CONCLUSION: The new model with a combination of rapid pacing and forced desynchronization of the ventricular contraction is superior to traditional heart failure models induced solely by rapid pacing.

Classically and alternatively activated macrophages contribute to tissue remodelling after myocardial infarction.

An important goal in cardiology is to minimize myocardial necrosis and to support a discrete but resilient scar formation after myocardial infarction (MI). Macrophages are a type of cells that influence cardiac remodelling during MI. Therefore, the goal of the present study was to investigate their transcriptional profile and to identify the type of activation during scar tissue formation. Ligature of the left anterior descending coronary artery was performed in mice. Macrophages were isolated from infarcted tissue using magnetic cell sorting after 5 days. The total RNA of macrophages was subjected to microarray analysis and compared with RNA from MI and LV-control. mRNA abundance of relevant targets was validated by quantitative real-time PCR 2, 5 and 10 days after MI (qRT-PCR). Immunohistochemistry was performed to localize activation type-specific proteins. The genome scan revealed 68 targets predominantly expressed by macrophages after MI. Among these targets, an increased mRNA abundance of genes, involved in both the classically (tumour necrosis factor alpha, interleukin 6, interleukin 1beta) and the alternatively (arginase 1 and 2, mannose receptor C type 1, chitinase 3-like 3) activated phenotype of macrophages, was found 5 days after MI. This observation was confirmed by qRT-PCR. Using immunohistochemistry, we confirmed that tumour necrosis factor alpha, representing the classical activation, is strongly transcribed early after ligature (2 days). It was decreased after 5 and 10 days. Five days after MI, we found a fundamental change towards alternative activation of macrophages with up-regulation of arginase 1. Our results demonstrate that macrophages are differentially activated during different phases of scar tissue formation after MI. During the early inflammatory phase, macrophages are predominantly classically activated, whereas their phenotype changes during the important transition from inflammation to scar tissue formation into an alternatively activated type.