Stefan Andreas

Improvement of exercise capacity with treatment of Cheyne-Stokes respiration in patients with congestive heart failure

OBJECTIVES The aim of this study was to determine the impact of nasal nocturnal oxygen therapy on respiration, sleep, exercise capacity, cognitive function and daytime symptoms in patients with congestive heart failure and Cheyne-Stokes respiration. BACKGROUND Cheyne-Stokes respiration is common in patients with congestive heart failure and is associated with significant nocturnal oxygen desaturation and sleep disruption with arousals. Oxygen desaturations and arousals cause an increase in pulmonary artery pressure and sympathoneural activity and therefore may reduce exercise capacity. Oxygen is an effective treatment of Cheyne-Stokes respiration and should improve exercise capacity in these patients. METHODS The study was designed as a randomized crossover, double-blind, placebo-controlled trial: 22 patients were assigned to 1 week each of nocturnal oxygen and room air. After each week, polysomnography, maximal bicycle exercise with expiratory gas analysis and trail-making test were performed, and a health assessment chart was completed. RESULTS Nocturnal oxygen significantly reduced the duration of Cheyne-Stokes respiration (162 +/- 142 vs. 88 +/- 105 min [mean +/- SD]; p < 0.005). Sleep improved as evidenced by less stage 1 sleep and fewer arousals (20 +/- 13 vs. 15 +/- 9/h total sleep time; p < 0.05) as well as more stage 2 and slow-wave sleep; nocturnal oxygen saturation also improved. Peak oxygen consumption during exercise testing increased after oxygen treatment (835 +/- 395 vs. 960 +/- 389 ml/min; p < 0.05). Cognitive function evaluated by the trail-making test improved, but daytime symptoms in the health assessment chart did not improve significantly. CONCLUSIONS Successful treatment of Cheyne-Stokes respiration with nocturnal nasal oxygen improves not only sleep, but also exercise tolerance and cognitive function in patients with congestive heart failure.

Cheyne-stokes respiration and prognosis in congestive heart failure

Patients with congestive heart failure (CHF) frequently demonstrate Cheyne-Stokes respiration (CSR) with repetitive arousals and oxygen desaturations during sleep. Although it was evident from early publications that CSR during the daytime is a poor prognostic indicator in patients with CHF, it was speculated recently that CSR occurring during sleep could impede left ventricular function and even survival. We therefore followed up 36 patients with CHF and a left ventricular ejection fraction < or = 40% who underwent a sleep study at our institution. The patients showed a reduced ejection fraction (20 +/- 8%) and CSR with a median of 19% of total sleep time (lower and upper quartiles 9% and 56%). In 12 +/- 9% of their time in bed, the arterial oxygen saturation was <90%. No patient was lost to follow-up, which lasted for 32 +/- 15 months (range 11 to 53). One-year survival was 86 +/- 6%, and 2-year survival was 66 +/- 8%. Univariate comparisons for survival between groups stratified by the amount of CSR revealed no significant difference (log rank test, p = 0.84). However, the 20 patients with a left ventricular ejection fraction <20% had a shorter mean survival time than patients with an ejection fraction >20% (9.5 vs 28.3 months; log rank test, p = 0.013). Two patients with CSR during the daytime died within 1 month. No other patient had CSR during the daytime, and only 1 patient without daytime CSR died within 1 month (chi-square test, p <0.001). Higher age, reduced carbon dioxide end-tidal partial pressure, and increased transit time were found to be significantly related to the amount of nocturnal CSR. In conclusion, CSR occurring during sleep has no important prognostic impact in patients with CHF, but CSR present during the daytime suggests a high likelihood of dying within a few months.

Infective endocarditis in the elderly in the era of transesophageal echocardiography: Clinical features and prognosis compared with younger patients

PURPOSE Advanced age is considered to be associated with a more severe prognosis in infective endocarditis (IE), which is relevance in view of a change in epidemiology of the disease with an increasing proportion of elderly people. We wanted to examine whether in the era of improved diagnostic sensitivity for IE by transesophageal echocardiography the clinical course in elderly persons would be still more severe than in younger patients. PATIENTS During the period from 1989 to 1993, 104 patients with 106 episodes of IE were treated at our university hospital. Three groups were compared: group A with 28 patients younger than 50 years, group B with 58 patients aged 50 to 70, and group C with 20 patients older than 70. Transesophageal echocardiography was performed in 78% of the patients; it was not performed in 22% of the patients with a conclusive transthoracic examination. The patients were followed up for an average of 25 months after the diagnosis. RESULTS No significant differences were observed among the age groups with respect to the possible source of infection, the frequency of positive blood cultures, and the type of infective organisms. Elderly patients more often had predisposing valvular conditions (eg, degenerative and calcified lesions and prosthetic valves), which decreased the sensitivity of transthoracic echocardiography to 45% as compared with 75% in group A. Transesophageal echocardiography improved the diagnostic yield by 45% in group C and by 47% in group B. Vegetations were smaller in group C and B as compared with group A, whereas other echocardiographic characteristics were similar. Fever and leukocytosis were less frequent in group C (55% and 25%, respectively) than in group A (82% and 61%, respectively). The interval between the onset of symptoms and the diagnosis of IE was similar in all groups. Elderly patients underwent surgical therapy as frequently (65%) as the other groups. The 1-year survival in group C (26%) was comparable with that in group A (22%) and group B (22%). The major determinant of survival was the occurrence of embolic complications. CONCLUSION Infective endocarditis in elderly patients caused less severe clinical symptoms than in young patients. The early diagnosis in elderly patients was facilitated by the high sensitivity of transesophageal echocardiography, which enabled the timely initiation of an appropriate medical and surgical therapy. This led to a clinical outcome similar to that for younger patients.

[Prevention, diagnosis, therapy, and follow-up of lung cancer].

Authors G. Goeckenjan1, H. Sitter2, M. Thomas3, D. Branscheid4, M. Flentje5, F. Griesinger6, N. Niederle7, M. Stuschke8, T. Blum9, K.-M. Deppermann10, J. H. Ficker11, L. Freitag12, A. S. Lübbe13, T. Reinhold14, E. Späth-Schwalbe15, D. Ukena16, M. Wickert17, M. Wolf18, S. Andreas19, T. Auberger20, R. P. Baum21, B. Baysal22, J. Beuth23, H. Bickeböller24, A. Böcking25, R. M. Bohle26, I. Brüske27, O. Burghuber28, N. Dickgreber29, S. Diederich30, H. Dienemann31, W. Eberhardt32, S. Eggeling33, T. Fink34, B. Fischer35, M. Franke36, G. Friedel37, T. Gauler38, S. Gütz39, H. Hautmann40, A. Hellmann41, D. Hellwig42, F. Herth43, C. P. Heußel44, W. Hilbe45, F. Hoffmeyer46, M. Horneber47, R. M. Huber48, J. Hübner49, H.-U. Kauczor50, K. Kirchbacher51, D. Kirsten52, T. Kraus53, S. M. Lang54, U. Martens55, A. Mohn-Staudner56, K.-M. Müller57, J. Müller-Nordhorn58, D. Nowak59, U. Ochmann59, B. Passlick60, I. Petersen61, R. Pirker62, B. Pokrajac63, M. Reck64, S. Riha65, C. Rübe66, A. Schmittel67, N. Schönfeld68, W. Schütte69, M. Serke70, G. Stamatis71, M. Steingräber72, M. Steins73, E. Stoelben74, L. Swoboda75, H. Teschler76, H. W.Tessen77, M. Weber78, A. Werner79, H.-E. Wichmann80, E. Irlinger Wimmer81, C. Witt82, H. Worth83

Slow breathing reduces sympathoexcitation in COPD.

Neurohumoral activation has been shown to be present in hypoxic patients with chronic obstructive pulmonary disease (COPD). The aims of the present study were to investigate whether there is sympathetic activation in COPD patients in the absence of hypoxia and whether slow breathing has an impact on sympathoexcitation and baroreflex sensitivity. Efferent muscle sympathetic nerve activity, blood pressure, cardiac frequency and respiratory movements were continuously measured in 15 COPD patients and 15 healthy control subjects. Baroreflex sensitivity was analysed by autoregressive spectral analysis and the alpha-angle method. At baseline, sympathetic nerve activity was significantly elevated in COPD patients and baroreflex sensitivity was decreased (5.0±0.6 versus 8.9±0.8 ms·mmHg−1). Breathing at a rate of 6 breaths·min−1 caused sympathetic activity to drop significantly in COPD patients (from 61.3±4.6 to 53.0±4.3 bursts per 100 heartbeats) but not in control subjects (39.2±3.2 versus 37.5±3.3 bursts per 100 heartbeats). In both groups, slow breathing significantly enhanced baroreflex sensitivity. In conclusion, sympathovagal imbalance is present in normoxic chronic obstructive pulmonary disease patients. The possibility of modifying these changes by slow breathing may help to better understand and influence this systemic disease.

Treatment of Cheyne-Stokes respiration with nasal oxygen and carbon dioxide

Cheyne-Stokes respiration (CSR) is common in patients with congestive heart failure (CHF) and is associated with significant nocturnal O2 desaturation, arousals and sympathetic activation. Nocturnal O2 reduces CSR by only about 50%. More complete suppression of CSR may be achieved by adding CO2 to O2. This study therefore aimed to evaluate the effects of nocturnal O2 plus CO2 on CSR, sleep and sympathetic activation. Nine patients with CHF (age 59+/-5 yrs; left ventricular ejection fraction 17.8+/-1.2% (mean+/-SEM) were studied in a cross-over, single-blind, placebo-controlled trial. After an accommodation night the patients were randomly assigned to one night each of O2 plus CO2 as well as air applied by nasal prongs. Nocturnal O2 plus CO2 reduced the duration of CSR as percentage of total sleep time (48.0+/-10 versus 7.4+/-2.0%; p=0.008) and increased arterial oxygen saturation (Sa,O2) as well as mean transcutaneous carbon dioxide tension (Ptc,CO2) (5.2+/-0.3 kPa (39+/-2 mmHg) versus 5.7+/-0.3 kPa (43+/-2 mmHg) p=0.011). Sleep did not improve and arousals were not reduced. Plasma noradrenaline was higher on the treatment night (486+/-116 versus 669+/-163 ng x L(-1); p=0.035). In conclusion, nocturnal O2 plus CO2 improves Cheyne-Stokes respiration in patients with congestive heart failure but has adverse effects on the sequel of Cheyne-Stokes respiration, namely sympathetic activation.

Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial

In chronic obstructive pulmonary disease (COPD), the sympathetic nervous system, as well as the renin–angiotensin system, is activated with possible negative systemic effects on skeletal muscles. Angiotensin II type-1 receptor blockers inhibit the sympathetic and renin–angiotensin systems and might improve skeletal and respiratory muscle strength in patients in whom these systems are activated. The effects of the angiotensin receptor blocker irbesartan given over 4 months was evaluated in 60 patients with COPD and a forced expiratory volume in one second of <50% of the predicted value and without obvious cardiovascular disease that would necessitate the administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Irbesartan was well tolerated, but did not exert a significant effect on the primary end-point maximum inspiratory pressure. Spirometric results were not affected, but total lung capacity was reduced. Irbesartan led to a significant decrease in haematocrit (46.4±3.6 to 43.9±4.3% versus 47.5±2.4 to 48.7±3.0% with placebo). In conclusion, respiratory muscle strength in chronic obstructive pulmonary disease patients was not influenced by angiotensin II receptor blockade. However, the changes in haematocrit and total lung capacity following irbesartan raise the possibility that well-known cardiovascular drugs can produce unanticipated beneficial effects in chronic obstructive pulmonary disease patients.

Pulmonary hypertension due to chronic lung disease: Updated Recommendations of the Cologne Consensus Conference 2011

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. These guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the use of these drugs in patients with chronic lung disease and PH is not recommended. This recommendation, however, is not always in agreement with medical needs as physicians feel sometimes inclined to also treat other forms of pulmonary hypertension which may affect the quality of life and survival of these patients in a similar manner as in PAH. In June 2010, a consensus conference was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology (DGK, DGP and DGPK). To this end, a number of working groups were initiated, one of which was specifically dedicated to the diagnosis and treatment of PH due to chronic lung disease. This manuscript describes in detail the results and recommendations of this working group which were last updated in October 2011.

Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit

Chronic obstructive pulmonary disease (COPD), lung cancer, asthma and pulmonary tuberculosis are common pulmonary diseases that are caused or worsened by tobacco smoking. Growing observational evidence suggests that symptoms and prognosis of these conditions improve upon smoking cessation. Despite increasing numbers of (small) randomised controlled trials suggesting intensive smoking cessation treatments work in people with pulmonary diseases many patients are not given specific advice on the benefits or referred for intensive cessation treatments and, therefore, continue smoking. This is a qualitative review regarding smoking cessation in patients with COPD and other pulmonary disorders, written by a group of European Respiratory Society experts. We describe the epidemiological links between smoking and pulmonary disorders, the evidence for benefits of stopping smoking, how best to assess tobacco dependence and what interventions currently work best to help pulmonary patients quit. Finally, we describe characteristics and management of any “hardcore” smoker who finds it difficult to quit with standard approaches. Smoking cessation is crucial for respiratory patients: every patient must be given advice and help to quit http://ow.ly/ITgsW

Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model

BackgroundSystemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease. We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease.MethodsFemale NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration.ResultsMean linear intercept was higher in emphysema (260.7 ± 26.8 μm) than in control lungs (24.7 ± 1.7 μm). Emphysema mice lost body weight, controls gained weight. Running distance was shorter in emphysema than in controls. Diaphragm muscle length was shorter in controls compared to emphysema. Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms. Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls. Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length.ConclusionThe elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation. The model may deepen our understanding of systemic aspects of COPD.