[Pathobiology, pathology and genetics of pulmonary hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Pathobiologie, Pathologie und Genetik der pulmonalen Hypertonie: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) are also valid for Germany. While the guidelines contain detailed recommendations regarding clinical aspects of pulmonary arterial hypertension (PAH) and other forms of PH, they contain only a relatively short paragraph on novel findings on the pathobiology, pathology, and genetics. However, these are of great importance for our understanding of this complex disease both from a clinical and scientific point of view, and they are essential for the development of novel treatment strategies. To this end, a number of current data are relevant, prompting a detailed commentary to the guidelines, and the consideration of new scientific data. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the pathobiology, pathology and genetics of PH. This article summarizes the results and recommendations of this working group.

[Pulmonary hypertension associated with left heart disease: recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Linksherzerkrankungen: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more common forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern because of limited ressources and the need to base treatments on scientific evidence. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, representing an unmet need of targeted PH therapies. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, several working groups were initiated, one of which was specifically dedicated to PH associated with left heart disease. This article summarizes the results and recommendations of this working group.

Methods for quantitative evaluation of alveolar structure during in vivo microscopy.

In vivo fibred confocal laser scanning microscopy allows an evaluation of differences in alveolar mechanics between healthy and acutely injured lungs during mechanical ventilation. The aim of this study was to develop new methods for a quantitative analysis of microscopic images in a murine model of experimental acute lung injury (ALI) and to assess the methods' portability to a large animal model. Differences observed in ALI compared to healthy lungs were: reduction of air-filled areas, increase of heterogeneity and increase of shape irregularity. Three indices were developed: the volume air index (VAI) applies an integral over specific signal intensities, the heterogeneity index (HI) and the Heywood circularity index (CI) comprise variances in size and shape of alveolar structures. The differences between healthy and ALI conditions were found to be significant for all of the used indices (VAI: 0.648 vs. 0.443 (p < 0.05), HI: 0.852 vs. 1.348 (p < 0.001) and CI: 1.56 vs. 1.66 (p < 0.001)). The portability of these algorithms to a porcine model was confirmed reaching similar results (VAI: 0.50 vs. 0.35, p < 0.05; HI: 0.62 vs. 1.83, p < 0.05; CI: 1.56 vs. 1.63, p < 0.001). VAI, HI and CI may help to quantify microscopic images of changes in alveolar structure after experimental ALI.

[Pulmonary hypertension due to left heart disease: recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei Linksherzerkrankungen: Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more frequent forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, so that it may be speculated whether selected patients may benefit from targeted PH therapy. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH due to left heart disease. This commentary summarizes the results and recommendations of this working group.

[Primary prevention of coronary heart disease with aspirin]. / Primäre Prävention der koronaren Herzkrankheit mit Aspirin.

According to meta-analysis and the results of the two studies with the highest power, aspirin is effective in primary prevention of coronary heart disease. These beneficial effects, however, are at least partially out-weight by unwanted effects-such as intense gastrointestinal bleeding and hemorrhagic stroke. These side effects remain constant with increasing risk of coronary heart disease, whereas the protective effects increase. If an annual risk of coronary heart disease of < or =0.6% exists, aspirin is normally not indicated; for a risk of 0.7-1.4% the facts should be discussed with the patient. If a risk of > or =1.5% exists, aspirin should be given. Problems of aspirin therapy--such as "aspirin paradox" and "aspirin resistance"--have been documented for secondary prevention; they might, however, have likewise clinical implications in primary prevention.

[Primary prevention of coronary heart disease? What is cost effective in the clinical practice?]. / Primärprävention der koronaren Herzerkrankung: Was ist in der Praxis bezahlbar?

In the primary prevention of coronary heart disease (CHD), the effect of aspirin and statins is well documented in several controlled randomized trials. For aspirin the results can be transferred into clinical practice due to its low price; for the more expensive statins, however, serious economic problems exist. In contrast to secondary prevention these drugs do not reach cost-efficiency in primary prevention; due to their high prices for the criteria of the randomized controlled studies values >60 000 or >100 000 [US dollars/YLS] are gained. Data from England and Scotland indicate that according to the inclusion criteria of the WOSCOPS- and AFCAPS/TexCAPS studies almost 20 and 60%, respectively, of the adult population had to be treated with a statin. Results of newer studies may even increase these numbers. These costs cannot be covered by any health care system. Primary prevention of CHD with statins reveals paradigmatically that for financial reasons evidence-based medicine can no longer be transferred into clinical practice. The limited resources of all health care systems make rationing with treatment allocation only to the high risk groups necessary. The American, European and German guidelines propose a > or =2% annual risk of CHD as the limit, for financial reasons the Britisch recommendations favor a limit of 3%; in order to save >50% of the costs. Despite the financial restraints of the German health care system, the limit of > or =2% annual risk of CHD as proposed by the German Cardiac Society may be realistic when the different preventive measures are applied following a step-by-step plan based on the costs. According to the Procam algorithms, persons without diabetes mellitus or familiar disposition, who in case of nicotine abuse have given up smoking and if hypertensive have blood pressure values within the therapeutic range, statins are only to be given under the following conditions: LDL-cholesterol > or =175 or > or =190 mg/dl, for a HDL-cholesterol < or =35 or < or =45 mg/dl, or triglyceride levels > or =200 or > or =175 mg/dl, respectively. Diabetics without CHD have the same risk as non-diabetics with CHD. Therefore, in diabetics the same measures should be taken for primary prevention as in non-diabetics for secondary prevention. Evaluation of cost-efficiency indicates that intensive blood sugar control as well as intensive antihypertensive treatment and application of statins are all cost-effective in primary prevention of diabetics.

Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension (IPAH) is a pulmonary vasculopathy of unknown aetiology. Dyspnoea, peripheral airway obstruction and inefficient ventilation are common in IPAH. Data on respiratory muscle function are lacking. This prospective single-centre study included 26 female and 11 male patients with IPAH in World Health Organization functional classes II-IV. Mean+/-SD pulmonary artery pressure was 48.6+/-16.9 in females and 53.1+/-22.9 mmHg in males; cardiac output was 3.7+/-1.3 and 4.2+/-1.7 L x min(-1). Maximal inspiratory pressure (PI,max) was lower in the female patients than in 20 controls (5.3+/-2.0 versus 8.2+/-2.0 kPa). In the male patients, PI,max was lower than in 25 controls (6.8+/-2.2 versus 10.5+/-3.7 kPa). Maximal expiratory pressure (PE,max) was lower in the female patients than in controls (6.2+/-2.6 versus 9.5+/-2.1 kPa), and in male patients as compared to controls (7.1+/-1.6 versus 10.3+/-3.9 kPa). There was no correlation between PI,max or PE,max and parameters of pulmonary haemodynamics or exercise testing. The ratio of mouth occlusion pressure within the first 0.1 s of inspiration and PI,max was higher in IPAH than in controls (females 0.067+/-0.066 versus 0.021+/-0.008; males 0.047+/-0.061 versus 0.023+/-0.016). In conclusion, this study provides the first evidence of inspiratory and expiratory muscle weakness in idiopathic pulmonary arterial hypertension. The pathomechanisms and the prognostic significance should be further investigated.

[Perspectives in cardiological research]. / Perspektiven der kardiologischen Forschung.

German cardiological research is confronted with increasing difficulties. Clinical research is restricted by regulations, such as the working hours protecting law, the revised version of the legal articles against corruption and acceptance of advantage as well as by many parts of law for the general frame of the university structures. In addition more and more administrative duties are tranferred to doctors engaged in research. Furthermore cardiology is at a disadvantage as only part of the net profits for cardiological services are tranferred to the responsible clinic. Likewise the facilities for cooperation are increasingly restricted, as basic science institutions originally allocated to cardiological research, are now devoted to other subjects and as many pharmaceutical firms have left the country. Cardiology in our country is practically not supported by private research organizations. Research projects are, therefore, predominantly financed by grants from the Bundeministerium für Bildung und Forschung and by the Deutsche Forschungsgemeinschaft. The financial resources for research in our country are declining and much smaller compared, e. g., to the USA. As a consequence of the shortage of resources not only are the weak projects turned down; it is feared that also the very innovative projects are likewise excluded for entering unknown territory. In periods of financial restrictions the central office and the experts evaluating the projects have a special responsibility, which cannot be met by technical objections, such as e. g., an "unsufficient impact factor". In order to improve the conditions for cardiological research the net profits for cardiological services should be transferred unrestricted to the responsible clinic. The acceptance rate of cardiologcal projects may be increased by more intensive cooperation. At the end, the principle of help by self-help also applies to cardiological research; the British Heart Foundation has developed into an impressive research-supporting organization in similarly difficult times.

[Primary prevention of coronary heart disease with aspirin]. / Primäre Prävention der koronaren Herzkrankheit mit Aspirin.

According to the meta-analysis and the results of the two studies with the highest power, aspirin is effective in primary prevention of coronary heart disease. These beneficial effects, however, are at least partially outweighed by unwanted effects-such as intense gastrointestinal bleeding and hemorrhagic stroke. These side effects remain constant with increasing risk of coronary heart disease, whereas the protective effects increase. If an annual risk of coronary heart disease of < or = 0.6% exists, aspirin is normally not indicated; for a risk of 0.7-1.4% the facts should be discussed with the patient. If a risk of > or = 1.5% exists, aspirin should be given.

Enhanced iodide transport after transfer of the human sodium iodide symporter gene is associated with lack of retention and low absorbed dose.

Transfer of the sodium iodide symporter (hNIS) has been proposed as a new principle of cancer gene therapy. Using clinically relevant doses of (131)I for the treatment of NIS-expressing prostate carcinoma cells, we investigated the kinetics and the absorbed doses obtained in these tumors. hNIS-expressing cell lines accumulated up to 200 times more iodide when compared to wild-type cells. However, a rapid efflux of the radioactivity (80%) occurred during the first 20 min after replacement of the medium. In rats, the hNIS-expressing tumors accumulated up to 20 times more iodide when compared to contralateral transplanted wild-type tumors. After 24 h and doses of 550, 1200 or 2400 MBq/m(2) hNIS-expressing tumors lost 89, 89 and 91% of the initial activity, respectively. Dosimetric calculations showed that 1200 MBq/m(2) resulted in 3+/-0.5 Gy (wild-type tumor 0.15+/-0.1 Gy) and 2400 MBq/m(2) resulted in 3.1+/-0.9 Gy (wild-type tumor 0.26+/-0.02 Gy). Although transduction of the hNIS gene induces iodide transport in rat prostate adenocarcinoma a rapid efflux occurs, which leads to a low absorbed dose in genetically modified tumors. With regard to a therapeutic application additional conditions need to be defined leading to iodide trapping.

[Quo vadis cardiologia? Or: An nescis, mi fili, quantilla prudentia mundus regatur? (Pope Julius III)]. / Quo vadis cardiologia? Oder: An nescis, mi fili, quantilla prudentia mundus regatur? paragraph sign (Papst Julius III).

In order to recognize and to solve problems, a look in the future is essential despite many uncertainties. Besides sound bed side-teaching, the main aim in the education of the students should be to acquire self-responsiveness and an attitude of permanent learning. It is more than doubtful whether the high expectations of health politicians will be met to limit the cost of in-patient treatment by introducing diagnosis-related groups in combination with evidence-based medicine, as this method has several severe limitations in order to fulfill this duty. The new financial system based on diagnosis-related groups will be in favor of private investors compared to the government-dependent university hospitals. The changing population pyramid implies not only higher costs but in addition severe medical problems. Within the changing society, alterations in the patient's behavior are to be expected. Several factors will contribute to make the doctor's profession less attractive. In the developing countries a rapid increase in the non-communicative diseases, i.e., in coronary heart disease, has to be expected. Apart from the prolongation of life - especially during its terminal phase - it is mainly the allocation of resources between industrialized and developing countries which will determine the ethical discussion. Germany has lost its leading position of the 19th and beginning of the 20th century in medical sciences. This was based on the liberal university system introduced by Wilhelm von Humboldt. Several pioneering innovations of German cardiologists during the 20th century have not strengthened German industry - in contrast to the situation in the 19th century. The general conditions in Germany, which are not research oriented, have prompted the majority of the pharmaceutical firms to transfer their research activities into foreign countries. In addition Germany's cardiological research has lost basic sciences partners for clinically orientated basic research, as many institutes which formerly worked in the cardiovascular field, are now devoted to other specialties. Restrictive legal regulations--such as the law regulating working hours, anti-corruption laws and the new legal university framework--are not conducive to internationally competitive research. Creative and innovative research requires liberal general conditions and cannot be planed.

Heart rate variability enhances the prognostic value of established parameters in patients with congestive heart failure.

This prospective study evaluated whether heart rate variability (HRV) assessed from Holter ECG has prognostic value in addition to established parameters in patients with congestive heart failure (CHF). The study included 222 patients with CHF due to dilated or ischemic cardiomyopathy (left ventricular ejection fraction LVEF 21+/-1%; mean+/-SEM). During a mean follow-up of 15+/-1 months, 38 (17%) patients died and 45 (20%) were hospitalized due to worsening of CHF. The HRV parameter SDNN (standard deviation of all intervals between normal beats) was significantly lower in non-surviving or hospitalized than in event-free patients (118+/-6 vs 142+/-5 ms), as were LVEF (18+/-1 vs 23+/-1%), and peak oxygen uptake during exercise (peak VO(2)) (12.8+/-0.5 vs 15.6+/-0.5 ml/min/kg). While each of these parameters was a risk predictor in univariate analysis, multivariate analysis revealed that HRV provides both independent and additional prognostic information with respect to the risk 'cardiac mortality or deterioration of CHF'. It is concluded that the determination of HRV enhances the prognostic power given by the most widely used parameters LVEF and peak VO(2) in the prediction of mortality or deterioration of CHF and thus enables to improve risk stratification.

[Secondary and primary prevention of coronary heart disease: platelet aggregation inhibitors and anticoagulants]. / Sekundäre und primäre Prävention der koronaren Herzerkrankung: Aggregationshemmer und Antikoagulantien.

This review presents the results of primary and secondary prevention of coronary heart disease (CHD) with antiplatelet drugs and anticoagulants; therapeutic recommendations are derived. According to the results of the trials and due to its low price aspirin (ASS) can be still considered as the drug of choice. Its protective action has been documented for secondary prevention in patients with previous myocardial infarction, coronary angioplasty (PCI), unstable and stable angina, but not in patients with coronary artery bypass surgery, heart failure as well as in primary prevention. The doses recommended are 75-325 mg/d. If ASS is not tolerated clopidogrel is an alternative, but an expensive one. Anticoagulation for primary prevention of CHD may be considered in high risk patients, who do not tolerate ASS (alternative: clopidogrel). In secondary prevention anticoagulation is only recommended for special conditions, such as ASS intolerance (alternative: clopidogrel), ventricular aneurysm, ventricular thrombus, severe heart failure and/or atrial fibrillation.

[Cardiomyopathy associated with uncontrolled self medication of anabolic steroids]. / Kardiomyopathie assoziiert mit unkontrollierter Selbstmedikation anaboler Steroide.

Though doping has become increasingly ostracized in the context of professional sports, an enormous number of unrecorded cases must be assumed in semi-professional competitive sports as well as in popular sports. This holds especially true for those forms of sports which are done in order to obtain a well-proportioned, athletic, healthy looking body. This case report describes a formerly healthy young man who had to be urgently admitted to an intensive care unit due to severe myocardial pump failure. As anamnestic information was insufficient and inadequate, the taking of anabolic steroids in high doses was proven, as their metabolites could be detected by urine analysis. Until now, myocardial contractile dysfunction has persisted for more than twelve months after the initial admission. Though other diagnoses which might have led to this impaired myocardial contractile performance have been excluded, cardiomyopathy associated with the taking of anabolic steroids must be assumed. Even in non-professional and public sports, a widespread abuse of doping substances exists. Hence, cardiomyopathy associated with the misuse of anabolic steroids has to be considered especially in young, formerly healthy patients.