[Differential Diagnosis of Pulmonary Hypertension Using the Example of Collagenosis-associated PAH in the Context of Chronic Lung and Left Heart Disease]. / Differenzialdiagnostik der pulmonalen Hypertonie am Beispiel der Kollagenose assoziierten PAH im Kontext chronischer Lungen- und Linksherzerkrankungen.

Pulmonary hypertension (PH) can be diagnosed in the context of connective tissue diseases (CTD) as well as in elderly patients with multiple comorbidities. A correct clinical differential diagnosis and classification is essential before adequate therapeutic decisions can be made. Differential diagnosis of PH in CTD comprises associated pulmonary arterial hypertension (APAH), group 2 or 3 PH (PH arising from left heart or chronic lung disease), chronic thromboembolic PH (PH) and group 5 (e. g. in the context of terminal renal insufficiency). This is also true of elderly patients in whom the decision has to be made if the increasing number of coincident diseases lead to PH or have to be interpreted as comorbidities. In this manuscript, the differential diagnosis of PH is elucidated, focusing on CTD, in the context of left heart disease and chronic lung disease. Furthermore, criteria are presented facilitating an objective approach in this context.

[Puzzling B symptoms in a 61-year-old patient under treatment for rheumatoid arthritis]. / Rätselhafte B-Symptomatik bei einem 61-Jährigen unter Therapie einer rheumatoiden Arthritis.

A patient with rheumatoid arthritis and immunosuppression developed symptoms of wasting, neuropathy and lung cavitations eventually leading to central nervous system symptoms and fatal multi-organ failure. Disseminated infection with Histoplasma capsulatum proved to be the underlying cause. The primary infection had apparently been acquired 4 years earlier on a holiday to the Caribbean. Rare infectious diseases should be considered in patients under immunosuppression and travel activities to specific endemic areas.

[Current Aspects of Definition and Diagnosis of Pulmonary Hypertension]. / Aktuelle Definition und Diagnostik der pulmonalen Hypertonie.

At the 6th World Symposium on Pulmonary Hypertension (WSPH), which took place from February 27 until March 1, 2018 in Nice, scientific progress over the past 5 years in the field of pulmonary hypertension (PH) was presented by 13 working groups. The results of the discussion were published as proceedings towards the end of 2018. One of the major changes suggested by the WSPH was the lowering of the diagnostic threshold for PH from ≥ 25 to > 20 mmHg mean pulmonary arterial pressure, measured by right heart catheterization at rest. In addition, the pulmonary vascular resistance was introduced into the definition of PH, which underlines the importance of cardiac output determination at the diagnostic right heart catheterization.In this article, we discuss the rationale and possible consequences of a changed PH definition in the context of the current literature. Further, we provide a current overview on non-invasive and invasive methods for diagnosis, differential diagnosis, and prognosis of PH, including exercise tests.

[Pulmonary hypertension: Possible genetic causes and therapeutic options]. / Pulmonale Hypertonie : Mögliche genetische Ursachen und therapeutische Optionen.

Pulmonary hypertension (PH) is a severe disease, which is usually only recognized at a late stage. It is characterized by dyspnea and right heart insufficiency. In some forms of pulmonary hypertension, such as the rare pulmonary arterial hypertension (PAH) and PAH associated with congenital heart defects, genetic factors have been identified. This article summarizes the general and supportive therapies for PH, targeted pharmaceutical treatment for PAH and non-operable chronic thromboembolic pulmonary hypertension. To achieve acceptable survival rates, it is essential to transfer patients to an expert center at an early stage for further differential diagnostics and therapy.

[Therapy of Pulmonary Arterial Hypertension]. / Therapie der pulmonal arteriellen Hypertonie.

Pulmonary hypertension (PH) is classified into five distinct groups according to the fifth world conference in Nice 2013. Pulmonary arterial hypertension (PAH) comprises idiopathic PAH, hereditary PAH, drug-induced and associated PAH. Right heart catheterization is essential for the diagnosis of PH and should precede initiation of a targeted PAH therapy. Besides general measures and supportive therapy, four different classes of targeted drugs have been approved for the treatment of PAH. Combination therapy, either sequential or initial (up-front), is increasingly gaining recognition. Risk stratification and treatment goals have been defined to guide therapeutic decisions. However, cure is still far from reach and lung transplantation is an important treatment option for patients with end-stage disease under optimal supportive and targeted drug therapy.

[Riociguat: stimulator of soluble guanylate-cyclase. New mode of action for the treatment of pulmonary arterial and non operable chronic thromboembolic pulmonary hypertension]. / Riociguat: Stimulation der löslichen Guanylatzyklase. Neuer Wirkmechanismus zur Behandlung der pulmonal-arteriellen und der nicht operablen chronisch thromboembolischen pulmonalen Hypertonie.

Riociguat is the first clinically available soluble Guanylate-cyclase stimulator (sGC) and representative of a completely new class of drugs. Riociguat is approved for pulmonary arterial hypertension (PAH) and non-operable or recurrent/persistent chronic thromboembolic pulmonary hypertension (CTEPH). Moreover, Riociguat is currently under investigation for a wider spectrum of diseases. This article focusses on its mode of action and clinical trial data. Finally, based on these data, the status of approval, as well as the costs a proposal is given how Riociguat can be integrated in the current treatment of PAH and CTEPH.

[Dyspnoea in Patients with Pulmonary Hypertension (PH) - a Survey in Spezialized German PH Centres]. / Dyspnoe bei Patienten mit Pulmonaler Hypertonie (PH) - Ergebnisse einer Befragung in deutschen PH-Zentren.

Dyspnoea is the predominant symptom in patients with pulmonary hypertension (PH) at diagnosis. However, since dyspnoea is nonspecific and often occurs in a number of common diseases, the presence of PH can easily be underdiagnosed.In addition, this symptom underlies a high variability in the subjective perception, therefore further diagnostic procedures are often delayed by the patients.A survey of the incidence and severity of dyspnoea in 372 patients with PAH was conducted by questionnaire in German centres. Age, sex distribution and the range of comorbidities corresponded to the findings of national and international registries.Approximately 99 % of patients reported the presence of dyspnoea on exertion, even at low loads.Remarkably, in 13 % of patients dyspnoea occurs as a paroxysmal symptom, which may lead to the differential diagnosis of bronchial asthma. In addition, the patients who were being followed in specialized PH centres reported an increase in dyspnoea during the last year.The results of the survey on the incidence of dyspnoea in patients with PAH are consistent with the findings of international studies.

[Utility of invasive diagnostics in acute lung injury]. / Stellenwert der invasiven Diagnostik beim akuten Lungenversagen.

Acute lung injury/acute respiratory distress syndrome (ARDS) may be induced by a variety of disease entities. Apart from supportive treatment including lung protective ventilation, identification of the underlying process is of crucial importance for optimal therapeutic results. Usually the cause of ARDS can be identified by history, laboratory and radiologicial tests. In some cases a diagnosis cannot be made in spite of an extensive, less invasive diagnostic work-up. In these situations the risks of empirical treatment have to be balanced against the procedural risk of invasive diagnostics, namely open lung biopsy. Today, reports on more than 500 lung biopsies performed in selected ARDS patients are available showing a relevant diagnostic yield at an acceptable procedure-associated risk. Intensive care physicians should be aware of this diagnostic instrument, which can represent the decisive diagnostic step in patients with ARDS of unknown origin.

[Heart rate measurement for determination of training intensity in outpatient pulmonary sport groups]. / Herzfrequenzmessung zur Bestimmung der Trainingsintensität in Lungensportgruppen.

BACKGROUND: Exercise training is an integral component of the management of patients with asthma and COPD. A training intensity of 60-80% of maximum oxygen uptake (VO(2)max) has been recommended. Instead of ergospirometry measurement of heart rate can be used for training guidance. It is unknown whether the given target can be reached in outpatient training groups with substantial heterogeneity concerning diagnosis, disease severity, and age. METHODS AND PATIENTS: 61 adult patients (m = 15, w = 46; 63 +/- 9 years) with asthma (n = 50) or COPD (n = 11) exercised in groups of ambulant lung sports. An individualized target heart rate was calculated corresponding to an intensity of 60% to 80% of calculated VO(2)max which was equivalent to a heart rate from 97 to 137 beats per minute in the population studied. Heart rate, as a measure of the intensity of charge, was measured continuously with pulse frequency meters. RESULTS: All but one asthma patient exercised in the targeted heart rate range. Patients reached 81 +/- 9% of the training goal of calculated 80% VO(2)max (asthma patients: 79 +/- 9% vs. COPD patients: 88 +/- 9%, p < 0.005) No significant differences regarding training intensities were observed in relation to severity of illness or age. CONCLUSIONS: In outpatient lung sport groups of considerable heterogeneity regarding diagnosis, severity of illness and age, participants reach their individualized heart rate target range. COPD patients were training at a significantly higher relative training intensity. Heart rate is an easy to use parameter for training guidance.

[General and supportive therapy of pulmonary arterial hypertension]. / Allgemeine und supportive Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted and supportive treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-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, a number of working groups was initiated, one of which was specifically dedicated to general and supportive therapy of PAH. This article summarizes the results and recommendations of this working group.

[Targeted therapy of pulmonary arterial hypertension: Recommendations of the Cologne Consensus Conference 2016]. / Gezielte Therapie der pulmonal arteriellen Hypertonie: Empfehlungen der Kölner Konsensuskonferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-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, a number of working groups was initiated, one of which was specifically dedicated to the targeted therapy of PAH. This article summarizes the results and recommendations of the working group on targeted treatment of PAH.

[Pulmonary hypertension due to chronic lung disease: Recommendations of the Cologne Consensus Conference 2016]. / Pulmonale Hypertonie bei Lungenkrankheiten: Empfehlungen der Kölner Konsensus-Konferenz 2016.

The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. 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, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

Radiologic management of haemoptysis: diagnostic and interventional bronchial arterial embolisation.

UNLABELLED: Hemoptysis can be a life-threatening pulmonary emergency with high mortality, is symptomatic of an underlying severe pulmonary disease and requires immediate diagnosis and treatment. Diagnostically, bronchoscopy, conventional chest x-ray and contrast-enhanced multislice computed tomography (MSCT) with CT angiography (CTA) provide information regarding the underlying pulmonary disease, bleeding site, the vascular anatomy of the bronchial arteries (BA) and extrabronchial branches, as well a basis for planning of endovascular intervention. Therapeutically, bronchial artery embolization (BAE) is a safe and effective technique in the hands of an experienced interventionist with profound knowledge of the BA anatomy and possible pitfalls as well as experience with first-line therapy of recurrent and massive hemoptysis or as an intervention prior to elective surgery. Recurrent episodes of hemoptysis are not uncommon and require a prompt repeat BAE after exclusion of extrabronchial systemic and pulmonary artery bleeding sources. This review article should give an overview of the history, anatomical and pathophysiological basics and the clinical context of hemoptysis and diagnosis, as well as a survey of management, treatment and results of BAE. KEY POINTS: Hemoptyses are life threatening and require urgent diagnostic and therapy. Chest x-ray, bronchoscopy, and contrast-enhanced MSCT with CTA should be carried out before therapeutic bronchial artery embolization (BAE). BAE for the treatment of massive and recurrent hemoptysis is safe and effective. False embolization in spinal branches of BA are the most serious complication of a BAE. Repeatedly BAE refractory cases should undergo elective surgery.

Correlation of antibodies to LAV/HTLV III in hemophiliacs with the use of virus-inactivated clotting factors.

The retrovirus LAV/HTLV III, highly likely to be responsible for the acquired immunodeficiency syndrome (AIDS) in some recipients of blood products, can be inactivated by chemical and/or heat treatment, so the use of virus-inactivated factor VIII and factor IX preparations for treating hemophilia A and B has become important. We examined hemophilic children and found that those children treated since 1979 with virus-inactivated preparations did not develop antibodies against LAV/HTLV III. In contrast, 77% of patients treated with conventional factor VIII or factor IX preparations had antibodies against this virus.

Geometric mismatch between homograft (allograft) and native aortic root: a 14-year clinical experience.

OBJECTIVES: We evaluated the effect of homograft/native aortic root geometric matching and mismatching on valve survival and myocardial remodeling. METHODS: Between January 1, 1987 and March 2000, a total of 292 patients, aged 1.5-78 years (mean, 46.2 years), underwent freehand subcoronary aortic valve (AVR; n=207) and root (ARR; n=85) replacement with matched and mismatched cryopreserved homografts. All patients had pre- and postoperative two-dimensional Doppler echocardiographic studies. Two-hundred and forty-three survivors, excluding children with complete data on sizing, were followed at a total follow-up time of 1269 patient-years. Seventy percent received matched and 30% received mismatched aortic homografts. The homograft valve sizes ranged from 19 to 28 mm. RESULTS: Hospital death for elective first operation was 2.3%, and late death after a mean follow-up of 52 months was 7.9%. The patient survival at 14 years was 92+/-2%. By linear regression analysis, matched homografts were equal to or 1-2 mm less than the native aortic annulus (r(2)=0.73). The valve survival in patients with AVR and ARR was 72+/-4 and 80+/-8% at 14 years, respectively. The freedom from reoperation was 92+/-5, 77+/-4 and 48+/-10% at 14 years for matched, oversized and undersized homografts, respectively (P=0.001). The postoperative cardiac index of patients with 22 and 24 mm homografts was 3.8-4.1 l/m(2), and there was a regression of the left ventricular mass and end-diastolic diameter (P=0.001). CONCLUSIONS: The aortic homograft offers an excellent long-term clinical result. A mismatched homograft is a risk factor for postoperative aortic incompetence, reinfection with pseudoaneurysmal formation and reoperation for the freehand subcoronary implantation technique during the first 7 years of the postoperative period. It is prudent therefore to avoid mismatched homografts and use rather a properly sized stentless xenograft if a root replacement is not indicated.

Surgical management of acute aortic root endocarditis with viable homograft: 13-year experience.

OBJECTIVE: Cryopreserved homograft valves have been used for acute infective aortic root endocarditis with great success but it is compounded by its availability in all sizes. The long-term clinical results of geometric mismatched homografts are not well defined and addressed. METHODS: Over a 15-year period (April 1986-June 2001), 816 patients presented with active infective endocarditis. One hundred and eighty-two of the patients aged between 9 and 78 years (mean: 51.0 +/- 1.13 years) consisting of 142 males and 40 females received homograft aortic valves. One hundred and ten patients were in NYHA functional class III and 72 in class IV and in cardiogenic shock. Of the patients, 2.7% suffered from septic embolism. One hundred and twenty-four (68.1%) patients presented with periannular abscesses and 58 (31.9%) with no abscess while 107 native valve (NVE) and 75 prosthetic valve (PVE) endocarditis were diagnosed preoperatively by transesophageal echocardiography (TEE) and confirmed intraoperatively. Freehand subcoronary implantation (FSCI) was used in 106 patients and root replacement in 76 patients. RESULTS: The operative death was 8.5% and for patients in NYHA functional class IV and in cardiogenic shock was 14.5%. Late mortality rate was 7.9%. Patient survival after discharge from hospital at 1 year was 97% and at 10 years was 91%, respectively. Thirty-one (22.1%) patients underwent reoperation after 1.7 years (mean) with two deaths (6.4%). Early (< or = 60 days) and late reinfection rate was 2.7 and 3.6%, respectively. Freedom from reoperation for matched and undersized homografts at 10-13 years was 85 and 55%, respectively. The univariate model identified undersized homograft (P=0.002), FSCI (P=0.09) and reinfection (P=0.0001) as independent risk factors for developing early and late valve dysfunction resulting in reoperation and homograft explant. CONCLUSION: Early aggressive valve replacement with homograft for active infective aortic root endocarditis with periannular abscesses is more successful than delayed last resort surgery. Homografts exhibit excellent clinical performance and durability with a low rate of reinfection, if properly inserted. Undersized homograft is an incremental risk factor for early and late reoperation.

[Measuring carbon monoxide content in muscles]. / Zur Messung des Kohlenmonoxidgehaltes in der Muskulatur.

A method ist described to determine the CO-content in the tissue of muscles. The prepared tissue is pulverized in a swinging mill at the temperature of liquid nitrogen. Parts of the powder are weighed into headspace vessels. Carbon monoxide ist ejected by a formerly described method and measured gaschromatographically. The Fe-content is determined after an acid disintegration by AAS. Acute intoxications lead to higher CO-contents in heart than in periphere muscles. Chronic exposure to carbon monoxide does not produce these differences.

[Treatment of pulmonary arterial hypertension (PAH): recommendations of the Cologne Consensus Conference 2010]. / Therapie der pulmonal arteriellen Hypertonie (PAH): Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-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 the treatment of PAH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.