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.

Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions : Recommendations of the working group of interventional cardiology of the Netherlands Society of Cardiology.

INTRODUCTION: Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria. METHODS: Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring. RESULTS: Twenty-six indications were rated 'Appropriate', eighteen indications 'May be appropriate', and five 'Rarely appropriate'. Use of OCT was unanimously considered 'Appropriate' in stent thrombosis, and 'Appropriate' for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered 'Rarely Appropriate' on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery. CONCLUSIONS: The use of OCT in stent thrombosis is unanimously considered 'Appropriate' by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

[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.

[Procedural aspects in primary PCI: arterial access, stent selection, thrombectomy and treatment of non-culprit lesions]. / Prozedurale Aspekte im Rahmen der primären PCI: Arterieller Zugang, Stentselektion, Thrombektomie, Behandlung der Non-culprit-Läsionen.

Acute myocardial infarction was one of the most common causes of death in Germany in 2011. According to the guidelines of the European Society for Cardiology, systemic fibrinolysis and primary percutaneous coronary intervention (PCI) are the methods of choice for acute treatment. Primary PCI should be given priority due to its superiority. The transradial access should be preferred due to the lower bleeding complication rate. In the selection of stents the new generation of drug-eluting stents (DES) are superior to the first generation of bare metal stents (BMS). It has now been demonstrated that the incident rates of DES (e.g. mortality, target vessel revascularization, early and late stent thrombosis and myocardial infarction) are significantly lower. For bioresorbable scaffolds (BRS) long-term results for the use in treatment of ST-elevation myocardial infarction (STEMI) are not yet available but initial results are very promising. However, the selection of a stent needs to be done on an individual basis in order to do justice to all aspects. Data with respect to thrombectomy in acute treatment are heterogeneous. Currently, a thorough consideration of all aspects is necessary because thrombus aspiration can also be associated with an increased rate of incidents. In a state of hemodynamic stability only so-called culprit lesions should currently be treated with a stent. Elective interventions on further stenoses should be carried out after consideration of individual factors and if necessary evaluation of the hemodynamic relevance.

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.

[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.

Effects of 2-deoxy-D-glucose on proliferation of vascular smooth muscle cells and endothelial cells.

2-Deoxy-D-glucose (2-DG) is a glucose analogue that has been proposed for cancer therapy due to its cytostatic properties. Its effect on the proliferation of smooth muscle cells and endothelial cells has not been fully clarified. The aims of this study were to investigate the effects of 2-DG on the proliferation of porcine aortic endothelial cells (PAEC) and porcine smooth muscle cells (PSMC), to establish an overview of its dose-dependent inhibitory capacity and to examine whether the short-term incubation of cells with 2-DG has an impact on cell proliferation in culture. Our results showed a dose-dependent significant inhibitory effect on proliferation, which was more pronounced in PSMC than in PAEC. Even after short-term incubation of cells with 2-DG, relevant inhibition of proliferation was documented. The clinical application of 2-DG might be a promising concept by inhibiting cells that show a potentially rapid proliferation in response to non-malignant stimuli, such as smooth muscle cells after intracoronary stenting.

Negative inotropic effect of rapamycin on isolated human cardiomyocytes.

Rapamycin is an increasingly important immunosuppressive drug and reduces restenosis after coronary stenting, but its effects on cardiac contractility are largely unknown. We investigated the acute inotropic effects of rapamycin on isolated human cardiomyocytes. Cardiomyocytes were enzymatically isolated from right atrial appendages obtained during routine coronary artery bypass surgery. Cell morphology was examined by confocal microscopy. Cell contraction was recorded after electrical stimulation. Rapamycin elicited a concentration-dependent decrease in fractional cell shortening ranging from 14.3 +/- 2.6% at 10(-8) M rapamycin to 26.4 +/- 4.2% at 10(-5) M. Rapamycin also caused a concentration-dependent decrease in diastolic cell length. Contractile performance of isolated cardiomyocytes was well preserved, as evidenced by the profound positive inotropic effects of high extracellular calcium concentration and the beta-adrenoreceptor agonist isoproterenol. The acute negative inotropic effect of rapamycin on human cardiomyocytes might be due to altered calcium homeostasis through the binding of rapamycin to FKBP12.6 and its regulatory function on the ryanodine receptor, with increased calcium leakage from the sarcoplasmic reticulum.

[Tako-Tsubo-cardiomyopathy]. / Tako-Tsubo-Kardiomyopathie.

Tako-Tsubo cardiomyopathy (TTC) is a heart syndrome associated with transient contractile dysfunction. It is also referred to as "broken heart syndrome" or "transient left ventricular apical ballooning." Leading symptom is a sudden onset of chest pain, often accompanied by dyspnoea. Clinical features include new electrocardiographic changes (ST-Segment elevations, T wave inversions), moderate elevation of the cardiac enzymes and transient wall motion abnormalities in absence of significant coronary artery obstruction. Although causal treatment has not been established, TTC has a favourable prognosis with a low mortality and a complete recovery of the contractile function in nearly all cases. Although several mechanisms have been proposed, the pathophysiology is not yet fully understood. However, emotional and physical stress followed by excessive release of catecholamines might play a pivotal role in the development of TTC.

Left ventricular tamponade - a clinical chameleon.

We present a 45-year-old patient who had to undergo aortocoronary bypass surgery after acute posterior myocardial infarction. On day twelve, the patient suddenly developed the classic signs of cardiogenic shock including angina, tachycardia, and hypotension. ECG displayed significant ST-elevations and troponin T was positive. Echocardiography suspected relevant pericardial effusion. However, the typical clinical signs of acute pericardial tamponade(distension of jugular veins, paradoxical pulse) were absent. Therefore, a computed tomography was carried out, which confirmed an isolated left ventricular tamponade resulting in severe diastolic and systolic dysfunction with profoundly impaired left ventricular filling. Immediate operative drainage was necessary since percutaneous pericardiocentesis was impossible given the untypical localization. This case demonstrates that clearcut signs of myocardial infarction can be misleading and may represent the untypical presentation of left ventricular tamponade,particularly in the setting after open-heart surgery.