Stephan Schroll

Prognostic impact of sleep disordered breathing and its treatment in heart failure: an observational study

Sleep disordered breathing (SDB) may contribute to disease progression in patients with chronic heart failure (CHF). The objective of this observational study was to evaluate whether SDB is a risk factor for mortality in CHF patients and whether this risk can be attenuated by treatment with positive airway pressure (PAP).

Impact of right ventricular reserve on exercise capacity and survival in patients with pulmonary hypertension.

Pulmonary hypertension is a clinical syndrome characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are key subgroups of this disorder with comparable clinical and pathological findings. Resting pulmonary haemodynamics correlate only moderately with functional parameters and do not predict prognosis in these patients sufficiently accurately. We therefore correlated exercise haemodynamics with peak oxygen uptake (peakVO2) and determined their prognostic significance.

Auto-servoventilation in heart failure with sleep apnoea: a randomised controlled trial

We tested the hypotheses that in patients with congestive heart failure (CHF) and sleep disordered breathing (SDB) auto-servoventilation (ASV) improves cardiac function and quality of life. Between March 2007 and September 2009, patients with stable CHF (left ventricular ejection fraction (LVEF) ≤40%) and SDB (apnoea/hypopnoea index ≥20 events·h−1) were randomised to receive either ASV (BiPAP ASV (Philips Respironics, Murrysville, PA, USA), n=37) and optimal medical management, or optimal medical management alone (n=35). Outcomes were assessed at baseline and 12 weeks. The apnoea/hypopnoea index assessed with polysomnography scored in one core laboratory was significantly more reduced in the ASV group (-39±16 versus -1±13 events·h−1; p<0.001) with an average use of 4.5±3.0 h·day−1. Both groups showed similar improvements of the primary end-point LVEF (+3.4±5 versus +3.5±6%; p=0.915) assessed with echocardiography. In the ASV group, reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly greater (-360±569 versus +135±625 ng·mL−1; p=0.010). No differences were observed between the groups in subjective quality of life. In patients with CHF and SDB, ASV reduced NT-proBNP levels, but improvement of LVEF or quality of life was not greater than in the control group. The data support that such patients can be randomised in large-scale, long-term trials of positive airway pressure therapy versus control to determine effects on cardiovascular outcome. Patients with heart failure and sleep apnoea can be randomised in long-term trials of positive airway pressure therapy http://ow.ly/nQnVg

Impact of noninvasive home ventilation on long‐term survival in chronic hypercapnic COPD: a prospective observational study

Aims:  The long‐term benefit from noninvasive ventilation (NIV) in chronic hypercapnic chronic obstructive pulmonary disease (COPD) remains uncertain.

Improvement of bleomycin-induced pulmonary hypertension and pulmonary fibrosis by the endothelin receptor antagonist Bosentan

RATIONALE There is evidence that endothelin plays a key role in the development of pulmonary hypertension (PH) in pulmonary fibrosis (PF). However, the functional consequence of the unselective endothelin receptor antagonist Bosentan in PH and PF has not yet been studied. Therefore, we investigated the effects of Bosentan on the development of PH in the model of Bleomycin-induced PF in rats. METHODS Adult male Wistar rats were randomly assigned to the following groups: untreated animals (controls), Bleomycin-induced PF (Bleomycin) and Bleomycin-induced PF treated with Bosentan (Bleomycin+Bosentan). Exercise capacity was evaluated by treadmill exercise testing. PH was assessed by right ventricular systolic pressure (RVSP) and right ventricular hypertrophy. For quantification of PF the hydroxyproline content in lung tissue (HPC) was measured. RESULTS Compared to controls, animals with Bleomycin-induced PF showed a significant reduction in exercise capacity (44% vs. 100%), significantly higher RVSP (65 mmHg vs. 23 mmHg), significantly more right ventricular hypertrophy (0.55 vs. 0.24) and significantly higher HPC (60.5 vs. 14.8). Bosentan treatment in animals with Bleomycin-induced PF resulted in significantly greater exercise capacity (98% vs. 44%) and a trend towards lower RVSP (52 mmHg vs. 65 mmHg), significantly less right ventricular hypertrophy (0.34 vs. 0.55) and significantly lower HPC (16.7 vs. 60.5) compared to untreated Bleomycin-induced PF. CONCLUSION Application of Bosentan in Bleomycin rats resulted in significantly higher exercise capacity as a result of improvements in PH and PF.

Predictive Significance of the Six-Minute Walk Distance for Long-Term Survival in Chronic Hypercapnic Respiratory Failure

Background: The 6-min walk distance (6-MWD) is a global marker of functional capacity and prognosis in chronic obstructive pulmonary disease (COPD), but less explored in other chronic respiratory diseases. Objective: To study the role of 6-MWD in chronic hypercapnic respiratory failure (CHRF). Methods: In 424 stable patients with CHRF and non-invasive ventilation (NIV) comprising COPD (n = 197), restrictive diseases (RD; n = 112) and obesity-hypoventilation-syndrome (OHS; n = 115), the prognostic value of 6-MWD for long-term survival was assessed in relation to that of body mass index (BMI), lung function, respiratory muscle function and laboratory parameters. Results: 6-MWD was reduced in patients with COPD (median 280 m; quartiles 204/350 m) and RD (290 m; 204/362 m) compared to OHS (360 m; 275/440 m; p < 0.001 each). Overall mortality during 24.9 (13.1/40.5) months was 22.9%. In the 424 patients with CHRF, 6-MWD independently predicted mortality in addition to BMI, leukocytes and forced expiratory volume in 1 s (p < 0.05 each). In COPD, 6-MWD was strongly associated with mortality using the median [p < 0.001, hazard ratio (HR) = 3.75, 95% confidence interval (CI): 2.24–6.38] or quartiles as cutoff levels. In contrast, 6-MWD was only significantly associated with impaired survival in RD patients when it was reduced to 204 m or less (1st quartile; p = 0.003, HR = 3.31, 95% CI: 1.73–14.10), while in OHS 6-MWD had not any prognostic value. Conclusions: In patients with CHRF and NIV, 6-MWD was predictive for long-term survival particularly in COPD. In RD only severely reduced 6-MWD predicted mortality, while in OHS 6-MWD was relatively high and had no prognostic value. These results support a disease-specific use of 6-MWD in the routine assessment of patients with CHRF.

Time course of continuous positive airway pressure effects on central sleep apnoea in patients with chronic heart failure

Continuous positive airway pressure (CPAP) causes a variable immediate reduction in the frequency of central apnoeas and hypopnoeas in patients with congestive heart failure (CHF) and central sleep apnoea (CSA), but has beneficial mid‐term effects on factors known to destabilize the ventilatory control system. We, therefore, tested whether CPAP therapy leads, in addition to its short‐term effects on CSA, to a significant further alleviation of CSA after 12 weeks of treatment on the same CPAP level in such patients. CPAP therapy was initiated in 10 CHF patients with CSA. During the first night on CPAP, the pressure was stepwise increased to a target pressure of 8–12 cmH2O or the highest level the patients tolerated (<12 cmH2O). Throughout the second night (baseline CPAP), the achieved CPAP of the first night was applied. After 12 weeks of CPAP treatment, we performed a follow‐up polysomnography (12 weeks CPAP) on the same CPAP level (8.6 ± 1.1 cmH20). We found a significant reduction of the apnoea‐hypopnoea index (AHI) between the diagnostic polysomnography and baseline CPAP night (41.8 ± 19.2 versus 22.2 ± 12.6 events per hour; P = 0.005). The AHI further significantly decreased between the baseline CPAP night and the 12 weeks CPAP night on the same CPAP level (22.2 ± 12.6 versus 12.8 ± 11.0 events per hour; P = 0.028). We conclude that, in addition to its immediate effects, CPAP therapy leads to a time‐dependent alleviation of CSA in some CHF patients, indicating that in such patients neither clinical nor scientific decisions should be based on a short‐term trial of CPAP.

d-dimers as an early marker for oxygenator exchange in extracorporeal membrane oxygenation ☆ ☆☆

PURPOSE Early markers of oxygenator dysfunction during prolonged use of extracorporeal membrane oxygenation (ECMO) are important for timely exchange to avoid sudden loss of function due to clot formation within the system. The measurement of D-dimers (DDs) in plasma might be a marker for early diagnosis of thrombus formation and dysfunction of heparin-coated membrane oxygenators (MOs). METHODS This is a retrospective study on prospectively collected data of 24 adult acute respiratory distress syndrome patients requiring long-term veno-venous ECMO with at least 1 MO exchange. Kinetics of coagulation, inflammation, and oxygenator function were analyzed before and after MO exchange. RESULTS Median (interquartile range) support duration is 20 (15-29) days. Thirty-four MOs had to be replaced. Exchange occurred due to visible thrombus formation in the MO (n=16), worsening gas exchange (n=11), increased blood flow resistance (n=1), and activation of coagulation with diffuse bleeding (n=6). In 15 cases, DDs were continuously elevated and, therefore, not suitable as marker for MO exchange. In the remaining 19 cases, DDs increased significantly within 3 days before exchange from 15 (9-20) to 30 (21-35) mg/dL (P=.002) and declined significantly within 1 day thereafter to 13 (7-17) mg/dL (P=.003). CONCLUSIONS An increase in plasma DD concentration in absence of other explaining pathology can be helpful in predicting an MO exchange in miniaturized heparin-coated ECMO systems.

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin-treated rats

Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity in vitro and pulmonary hypertension in vivo. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin‐treated rats in vivo.

Improvement of exercise capacity in monocrotaline-induced pulmonary hypertension by the phosphodiesterase-5 inhibitor Vardenafil

Vardenafil, a phosphodiesterase-5 inhibitor, is approved for the therapy of erectile dysfunction. However, in contrast to Sildenafil and Tadalafil, little is known about its effects on pulmonary hypertension. Four weeks after monocrotaline-administration rats exhibited a significant increase in right ventricular pressure (RVSP, 94mmHg vs. 25mmHg; p=0.001) right ventricular weight (right ventricle/left ventricle+septum, 59 vs. 23; p=0.001) and pulmonary vascular remodeling (medial wall area 104% vs. 66%; p<0.05) as compared to controls, with a corresponding reduction in exercise capacity (% from baseline value: 67%; p<0.05). Vardenafil treatment resulted in decreased RVSP (56mmHg vs. 95mmHg; p=0.008), right ventricular weight (41 vs. 59; p=0.013), pulmonary vascular remodeling (medial wall area 64% vs. 104%; p<0.05) and a significant better exercise capacity (% from baseline value: 84% vs. 67%; p<0.05) compared to monocrotaline only treated animals. In conclusion, Vardenafil exerts beneficial effects on monocrotaline-induced pulmonary hypertension in rats. Whether it is a treatment option for patients with pulmonary hypertension needs to be elucidated.