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ABSTRACT: OBJECTIVES: Pilot studies have described the occurrence of sleep apnea in patients with precapillary pulmonary hypertension (PH). However, there are no data on the prevalence of sleep-related breathing disorders in larger patient cohorts with PH. METHODS: 169 patients with a diagnosis of PH confirmed by right heart catheterisation and clinically stable in NYHA classes II or III were prospectively investigated by polygraphy (n=105 females, mean age: 61.3years, mean body mass index: 27.2kg/m(2)). Recruitment was independent of sleep-related symptoms and the use of vasodilator drugs or nasal oxygen. RESULTS: 45 patients (i.e. 26.6%) had an apnea-hypopnea-index (AHI) >10/h. Of these, 27 patients (i.e. 16%) had obstructive sleep apnea (OSA) and 18 patients (i.e. 10.6%) had central sleep apnea (CSA). The mean AHI was 20/hour. As a polygraphy had been performed with nasal oxygen in half of the patients without evidence for sleep apnea, the frequency of CSA was probably underestimated. Patients with OSA were characterized by male gender and higher body mass index whereas, those with CSA were older and hypocapnic. CONCLUSIONS: At least every fourth patient with PH suffers from mild-to-moderate sleep apnea. Considering the anthropometric characteristics of the patients studied, the prevalence of both OSA and CSA seem to be higher in PH than in the general population.
Sleep Medicine 01/2013; · 3.40 Impact Factor
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Tabea Becker-Grünig,
Hans Klose,
Nicola Ehlken,
Mona Lichtblau,
Christian Nagel,
Christine Fischer,
Matthias Gorenflo, Henning Tiede,
Dietmar Schranz,
Alfred Hager,
Harald Kaemmerer,
Oliver Miera,
Silvia Ulrich,
Rudolf Speich,
Sören Uiker,
Ekkehard Grünig
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ABSTRACT: BACKGROUND: The objective of this prospective study was to assess the efficacy of exercise training as add-on to medical therapy in patients with congenital heart disease associated pulmonary arterial hypertension (CHD-APAH). METHODS: Patients with invasively confirmed CHD-APAH received in-hospital exercise training for 3weeks and continued at home. Efficacy parameters were evaluated at baseline, after 3 and 15weeks. Medical treatment remained unchanged. Worsening events and survival rate were assessed in a follow-up period of 21±14months. RESULTS: Twenty consecutive CHD-APAH patients (16 female, 4 male, mean pulmonary arterial pressure 60±23mmHg) were included. Patients significantly improved the mean distance walked in 6min compared to baseline by 63±47m after 3weeks (p<0.001) and by 67±59m after 15weeks (p=0.001). Quality of life-score (p=0.05), peak oxygen consumption (p=0.002) and maximal workload (p=0.003) improved significantly by exercise training after 15weeks. The 1- and 2-year survival rates were 100%, the transplantation-free survival rate was 100% after 1year and 93% after 2years. CONCLUSION: Exercise training as add-on to medical therapy may be effective in patients with CHD-APAH and improved work capacity, quality of life and further prognostic relevant parameters. It was associated with an excellent long-term survival. Further randomized controlled studies are needed to confirm these results.
International journal of cardiology 10/2012; · 7.08 Impact Factor
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ABSTRACT: Patients with pulmonary arterial hypertension (PAH) exhibit impaired glucose metabolism and increased insulin resistance. The clinical consequences of these metabolic changes are not known.
We assessed HbA(1c) levels in 115 patients newly diagnosed with PAH (79 females and 36 males; mean age 49.2 years; idiopathic n = 67, collagen vascular disease n = 16, congenital heart defect n = 19, pulmonary veno-occlusive disease n = 8, portopulmonary n = 5). No patients had diabetes or were receiving anti-diabetic medication or systemic steroids. After initiation of pulmonary vasoactive treatment, patients remained in long-term follow-up.
Initially, patients were in an advanced stage of disease (mean pulmonary arterial pressure 53 ± 18 mm Hg, cardiac index 2.3 ± 0.8 liters/min/m(2)) with a 6-minute-walk distance of 337 ± 123 meters, and in NYHA Functional Class 3.0 ± 0.7. The HbA(1c) was 5.73 ± 0.75%. A moderate but statistically significant positive correlation was observed between HbA(1c) levels and BNP (r(p) = 0.41, p = 0.014), but no correlation was found with hemodynamics or 6-minute-walk distance. The 5-year survival rate for the entire group was 68%. Kaplan-Meier analysis and multivariate Cox proportional hazard models correcting for demographic and clinical covariates revealed that patients with HbA(1c) <5.7% had a significantly better 5-year survival compared with those having higher initial values (85.1% vs 55.9%; log rank p = 0.002). HbA(1c) was a predictor of all-cause mortality with a hazard ratio of 2.23 (95% CI 1.06 to 4.70; p = 0.034) per 1-unit increase of HbA(1c).
In patients with pulmonary arterial hypertension, the HbA(1c) level at time of diagnosis is an independent predictor of long-term prognosis.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 10/2012; 31(10):1109-14. · 3.54 Impact Factor
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ABSTRACT: Patients with cystic fibrosis (CF) may suffer from sleep disturbances and reduced health-related quality of life (HRQoL). However, the relationships of daytime sleepiness and sleep quality to HRQoL in CF have not yet been investigated.
55 adult CF out-patients free from a pulmonary exacerbation were prospectively enrolled in this study. Questionnaires were used to assess disease-specific HRQoL (German version of the revised Cystic Fibrosis Questionnaire for adults, CFQ18 + R), daytime sleepiness (Epworth Sleepiness Scale, ESS) and sleep quality (Pittsburgh Sleep Quality Index, PSQI). 30 age- and sex-matched healthy volunteers served as a control group.
The prevalence of daytime sleepiness was higher in the CF than in the control group (ESS > 10; n = 11 [20%] vs. n = 2 [6.7%]; p < 0.01) as was reduced sleep quality (PSQI > 5; n = 21 [38.2%] vs. n = 1 [3.3%]; p < 0.01). Multiple regression analysis including age, gender, body mass index, lung function and pseudomonas status showed that higher PSQI scores significantly correlated with lower CFQ18 + R scores for vitality, emotional functioning, social, role, eating disturbances and digestive symptoms.
In clinically stable adult CF out-patients self-reported daytime sleepiness and poor sleep quality are more common than in age and sex-matched healthy controls. In addition, impaired sleep quality is related to reduced disease-specific HRQoL in CF.
Respiratory medicine 07/2012; 106(9):1244-9. · 2.33 Impact Factor
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Ekkehard Grünig,
Felicitas Maier,
Nicola Ehlken,
Christine Fischer,
Mona Lichtblau,
Norbert Blank,
Christoph Fiehn,
Frank Stöckl,
Felix Prange,
Gerd Staehler,
Frank Reichenberger, Henning Tiede,
Michael Halank,
Hans-Jürgen Seyfarth,
Simone Wagner,
Christian Nagel
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ABSTRACT: The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH).
Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years.
Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET.
ET as add-on to medical therapy is highly effective in patients with CTD-APAH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further randomized controlled studies are needed to confirm these results.
ClinicalTrials.gov: NCT00491309.
Arthritis research & therapy 06/2012; 14(3):R148. · 4.27 Impact Factor
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Christian F Opitz,
Rüdiger Blindt,
Friedrich Blumberg,
Mathias M Borst,
Leonhard Bruch,
Hanno H Leuchte,
Mona Lichtblau,
Christian Nagel,
Klaus Peters,
Stephan Rosenkranz,
Dietmar Schranz,
Dirk Skowasch, Henning Tiede,
Joachim Weil,
Ralf Ewert
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ABSTRACT: The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. 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 invasive hemodynamic evaluation of pulmonary hypertension. This manuscript describes in detail the results and recommendations of the working group which were last updated in October 2011.
International journal of cardiology 12/2011; 154 Suppl 1:S13-9. · 7.08 Impact Factor
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Lars Knudsen,
Alexander Schurawlew,
Nils Nickel, Henning Tiede,
Hossein A Ghofrani,
Heinrike Wilkens,
Ralf Ewert,
Michael Halank,
Hans Klose,
Carlos Bäzner,
Jürgen Behr,
Marius M Hoeper
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ABSTRACT: The majority of patients with idiopathic pulmonary arterial hypertension (IPAH) in functional classes II and III are currently being treated with non-parenteral therapies, including endothelin receptor antagonists (ERA), phosphodiesterase (PDE)-5 inhibitors, inhaled iloprost or combinations of these substances. If these treatments fail, current guidelines recommend the addition of parenteral prostanoid therapy. There is, however, limited evidence for the efficacy of parenteral prostanoids when added to combinations of non-parenteral therapies.
In this retrospective, multicentre study we collected data from consecutive IPAH patients receiving intravenous iloprost in addition to optimized non-parenteral therapy between Jan 2002 and Dec 2009. Analyses included 6 min walk distance (6MWD), functional class, need for transplantation, and survival.
During the observation period, 50 patients were treated with intravenous iloprost in addition to non-parenteral therapy; 44% of the patients were on dual combination therapy and 52% on triple combination. Three months after initiation of iloprost, functional class had improved in 24% of the patients and the median 6MWD had increased from 289 m to 298 m (n.s.). During the observation period, 22 patients (44%) died and 14 (28%) underwent lung transplantation. The probabilities of LuTx-free survival at 1, 3 and 5 years following iloprost initiation were 38%, 17% and 17%, respectively. A 6MWD < 300 m and persistent functional class IV at 3 months after initiation of intravenous iloprost were predictors of an adverse outcome.
In essence, late initiation of intravenous iloprost in IPAH patients who previously failed to respond to non-parenteral therapies appears to be of limited efficacy in the majority patients. Alternative therapeutic options are currently not available, underlying the need for the development of new drugs.
BMC Pulmonary Medicine 12/2011; 11:56. · 1.33 Impact Factor
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ABSTRACT: Patients with pulmonary arterial hypertension often present with a mild obstructive lung pattern, however, the functional consequences are not known.
We analysed flow volume loops during exercise in 61 patients with precapillary pulmonary hypertension (PH) (age 55 ± 14 years) in comparison with 21 patients with COPD (60 ± 12 years), 39 patients with pulmonary fibrosis (58 ± 11 years) and 38 healthy controls (HC) (39 ± 15 years). Inspiratory capacity (IC) was measured at rest, and during maximum exercise (max).
HC exhibited a stable IC of 3.0 ± 0.9 l at rest, and at max. A reduction in IC of 2.6 ± 0.8 l at rest to 2.0 ± 0.7 l at max was observed in patients with COPD. Patients with PH exhibited a significant reduction in IC from 2.3 ± 0.6 l at rest to 2.1 ± 0.6 l at max, while patients with pulmonary fibrosis exhibited a stable IC of 1.8 ± 0.6 at rest and 1.7 ± 0.6 l at max. In patients with PH, a weak negative correlation was drawn between the change in IC (%) and peak VO2 (r = -0.29, p = 0.01), as well as with PVR (r = -0.27, p = 0.02).
Patients with PH demonstrate a characteristic change in IC during exercise, which might contribute to impaired exercise tolerance.
Respiratory medicine 11/2011; 106(2):308-13. · 2.33 Impact Factor
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ABSTRACT: Previous studies have shown the prognostic benefit of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in pulmonary arterial hypertension (PAH) at time of diagnosis. However, there are only limited data on the clinical utility of serial measurements of the inactive peptide NT-pro-BNP in PAH. This study examined the value of serial NT-pro-BNP measurements in predicting prognosis PAH. We retrospectively analyzed all available NT-pro-BNP plasma samples in 198 patients who were diagnosed with World Health Organization group I PAH from January 2002 through January 2009. At time of diagnosis median NT-pro-BNP levels were significantly different between survivors (610 pg/ml, range 6 to 8,714) and nonsurvivors (2,609 pg/ml, range 28 to 9,828, p <0.001). In addition, NT-pro-BNP was significantly associated (p <0.001) with other parameters of disease severity (6-minute walking distance, functional class). Receiver operating curve analysis identified ≥1,256 pg/ml as the optimal NT-pro-BNP cutoff for predicting mortality at time of diagnosis. Serial measurements allowed calculation of baseline NT-pro-BNP (i.e., intercept obtained by back-extrapolation of concentration-time graph), providing a better discrimination between survivors and nonsurvivors than NT-pro-BNP at time of diagnosis alone (p = 0.010). Furthermore, a decrease of NT-pro-BNP of >15%/year was associated with survival. In conclusion, a serum NT-pro-BNP level ≥1,256 pg/ml at time of diagnosis identifies poor outcome in patients with PAH. In addition, a decrease in NT-pro-BNP of >15%/year is associated with survival in PAH.
The American journal of cardiology 09/2011; 108(11):1645-50. · 3.58 Impact Factor
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Nicole Pfarr,
Justyna Szamalek-Hoegel,
Christine Fischer,
Katrin Hinderhofer,
Christian Nagel,
Nicola Ehlken, Henning Tiede,
Horst Olschewski,
Frank Reichenberger,
Ardeschir H A Ghofrani,
Werner Seeger,
Ekkehard Grünig
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ABSTRACT: Mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene can lead to idiopathic pulmonary arterial hypertension (IPAH). This study prospectively screened for BMPR2 mutations in a large cohort of PAH-patients and compared clinical features between BMPR2 mutation carriers and non-carriers.
Patients have been assessed by right heart catheterization and genetic testing. In all patients a detailed family history and pedigree analysis have been obtained. We compared age at diagnosis and hemodynamic parameters between carriers and non-carriers of BMPR2 mutations. In non-carriers with familial aggregation of PAH further genes/gene regions as the BMPR2 promoter region, the ACVRL1, Endoglin, and SMAD8 genes have been analysed.
Of the 231 index patients 22 revealed a confirmed familial aggregation of the disease (HPAH), 209 patients had sporadic IPAH. In 49 patients (86.3% of patients with familial aggregation and 14.3% of sporadic IPAH) mutations of the BMPR2 gene have been identified. Twelve BMPR2 mutations and 3 unclassified sequence variants have not yet been described before. Mutation carriers were significantly younger at diagnosis than non-carriers (38.53 ± 12.38 vs. 45.78 ± 11.32 years, p < 0.001) and had a more severe hemodynamic compromise. No gene defects have been detected in 3 patients with HPAH.
This study identified in a large prospectively assessed cohort of PAH- patients new BMPR2 mutations, which have not been described before and confirmed previous findings that mutation carriers are younger at diagnosis with a more severe hemodynamic compromise. Thus, screening for BMPR2 mutations may be clinically useful.
Respiratory research 07/2011; 12:99. · 3.36 Impact Factor
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ABSTRACT: Our aim was to determine what proportion of patients with pulmonary hypertension (PH) has undertaken air travel contrary to the general medical advice and to characterize these patients according to disease severity and medical treatment. In cooperation with Pulmonale Hypertonie e.V., the German patient organization, a questionnaire was distributed. In total, 430 of 720 questionnaires were returned completed. Of the 179 patients who travelled at least once by air, the distribution of New York Heart Association functional classes I/ II/ III/ IV was 2/ 77/ 74/ 8, respectively; 83 patients were receiving monotherapy; 58 patients were receiving a combination of two or more therapies; 57 patients were on long-term ambulatory oxygen treatment; and 29 patients used supplemental oxygen while travelling. Overall, 20 adverse events were reported, mostly of mild to moderate severity (i.e., peripheral edema, dyspnea), with need of medical intervention in only 7 cases. The 251 patients who did not travel by air were, on average, in more advanced stages of disease and/or clinically unstable. In conclusion, a majority of patients (159 out of 179) did not experience any complications during or directly after the flight even though no special precautions were taken. Thus we conclude that for patients with PH in a stable clinical condition, air travel can be safe and well tolerated.
Pulmonary circulation. 04/2011; 1(2):239-43.
