[Risk Stratification in Patients with Pulmonary Arterial Hypertension under Treatment - Results of Four German Centers]. / Risikoänderung bei Patienten mit Pulmonaler Arterieller Hypertonie unter medikamentöser Therapie ­ Ergebnisse aus vier deutschen Zentren.

Risk stratification plays an essential role in the management of patients with pulmonary arterial hypertension (PAH). According to the current European guidelines the expected 1-year risk of mortality for PAH patients can be categorized as low, intermediate, or high, based on clinical, non-invasive and hemodynamic data.Data from 131 patients with incident PAH (age 64 ±â€Š14) and frequent comorbidities (in 66.4 %) treated between 2016 and 2018 at 4 German PH centers were analyzed. At baseline, most patients were classified as intermediate risk (76 %), 13.8 % as high risk and only 9.9 % as low risk.During follow-up while on treatment after 12 ±â€Š3 months (range 9-16 months) 64.9 % were still classified as intermediate risk (76 %), 14.4 % as high risk and 20.7 % as low risk.Survival at 12 and 24 months was 96 % and 82 % in the intermediate risk group, while only 89 % and 51 % of the high risk patients were alive at these time points. In contrast, all patients in the low risk category were alive at 24 months.Despite the availability of various treatment options for patients with PAH even in specialized centers only a minority of patients can be stabilized in the low risk group associated with a good outcome.

[Invasive Cardiopulmonary Exercise Testing: A Review]. / Übersicht über die Entwicklung der invasiven Spiroergometrie (iCPET).

Right heart catheterization (RHC) is the internationally standardized reference method for measuring pulmonary hemodynamics under resting conditions. In recent years, increasing efforts have been made to establish the reliable assessment of exercise hemodynamics as well, in order to obtain additional diagnostic and prognostic data. Furthermore, cardiopulmonary exercise testing (CPET), as the most comprehensive non-invasive exercise test, is increasingly performed in combination with RHC providing detailed pathophysiological insights into the exercise response, so-called invasive cardiopulmonary exercise testing (iCPET).In this review, the accumulated experience with iCPET is presented and methodological details are discussed. This complex examination is especially helpful in differentiating the underlying causes of unexplained dyspnea. In particular, early forms of cardiac or pulmonary vascular dysfunction can be detected by integrated analysis of hemodynamic as well as ventilatory and gas exchange data. It is expected that with increasing validation of iCPET parameters, a more reliable differentiation of normal from pathological stress reactions will be possible.

Monotherapy in patients with pulmonary arterial hypertension at four German PH centres.

BACKGROUND: Although combination therapy is the gold standard for patients with pulmonary arterial hypertension (PAH), some of these patients are still being treated with monotherapy. METHODS: We conducted a retrospective analysis at four German PH centres to describe the prevalence and characteristics of patients receiving monotherapy. RESULTS: We identified 131 incident PAH patients, with a mean age of 64 ± 13.8 years and a varying prevalence of comorbidities, cardiovascular risk factors and targeted therapy. As in other studies, the extent of prescribed PAH therapy varied with age and coexisting diseases, and younger, so-called "typical" PAH patients were more commonly treated early with combination therapy (48% at 4-8 months). In contrast, patients with multiple comorbidities or cardiovascular risk factors were more often treated with monotherapy (69% at 4-8 months). Survival at 12 months was not significantly associated with the number of PAH drugs used (single, dual, triple therapy) and was not different between "atypical" and "typical" PAH patients (89% vs. 85%). CONCLUSION: Although "atypical" PAH patients with comorbidities or a more advanced age are less aggressively treated with respect to combination therapy, the outcome of monotherapy in these patients appears to be comparable to that of dual or triple therapy in "typical" PAH patients.

Comparison between thermodilution and Fick methods for resting and exercise-induced cardiac output measurement in patients with chronic dyspnea.

Studies comparing thermodilution (TD) and the direct Fick method (dFM) for cardiac output (CO) measurement are rare. We compared CO measurements between TD (2-5 cold water injections), the dFM, and indirect Fick method (iFM) at rest and during exercise, and assessed the effect of averaging different numbers of TD measurements during exercise. This retrospective study included 300 patients (52.3% women, mean age 66 ± 11 years) having pulmonary hypertension (76.0%) or unexplained dyspnea. Invasive hemodynamic and gas exchange parameters were measured at rest (supine; n = 300) and during unloaded cycling (semi-supine; n = 275) and 25-W exercise (semi-supine; n = 240). All three methods showed significant differences in CO measurement (ΔCO) at rest (p ≤ 0.001; ΔCO > 1 L/min: 45.0% [iFM vs. dFM], 42.0% [iFM vs. TD], and 45.7% [TD vs. dFM]). ΔCO (TD vs. dFM) was significant during unloaded cycling (p < 0.001; ΔCO > 1 L/min: 56.6%) but not during 25-W exercise (p = 0.137; ΔCO > 1 L/min: 52.8%). ΔCO (TD vs. dFM) during 25-W exercise was significant when using one or two (p ≤ 0.01) but not three (p = 0.06) TD measurements. Mean ΔCO (TD [≥3 measurements] vs. dFM) was -0.43 ± 1.98 and -0.06 ± 2.29 L/min during unloaded and 25-W exercise, respectively. Thus, TD and dFM CO measurements are comparable during 25-W exercise (averaging ≥3 TD measurements), but not during unloaded cycling or at rest. Individual ΔCOs vary substantially and require critical interpretation to avoid CO misclassification.

Predictors of survival after prolonged weaning from mechanical ventilation.

PURPOSE: Weaning from mechanical ventilation is a key component of intensive care treatment; however, this process may be prolonged as some patients require care at specialised centres. Current data indicate that weaning from invasive mechanical ventilation is successful in approximately 65% of patients; however, data on long-term survival after discharge from a weaning centre are limited. MATERIALS AND METHODS: We analysed predictors of survival among 597 patients (392 men, mean age 68 ± 11) post-discharge from a specialised German weaning centre. RESULTS: Complete weaning from mechanical ventilation was achieved in 407 (57.8%) patients, and 106 patients (15.1%) were discharged with non-invasive ventilation; thus, prolonged weaning was successful in 72.9% of the patients. The one-year and five-year survival rates post-discharge were 66.5% and 37.1%, respectively. Age, duration of mechanical ventilation, certain clusters of comorbidities, and discharged with mechanical ventilation significantly influenced survival (p < .001). Completely weaned patients who were discharged with a tracheostomy had a significantly reduced survival rate than did those who were completely weaned and discharged with a closed tracheostomy (p = .004). CONCLUSIONS: The identified predictors of survival after prolonged weaning could support therapeutic strategies during patients' intensive care unit stay. Patients should be closely monitored after discharge from a weaning centre.

Exercise and fluid challenge during right heart catheterisation for evaluation of dyspnoea.

This prospective study compared exercise test and intravenous fluid challenge in a single right heart catheter procedure to detect latent diastolic heart failure in patients with echocardiographic heart failure with preserved ejection function. We included 49 patients (73% female) with heart failure with preserved ejection function and pulmonary artery wedge pressure ≤15 mmHg. A subgroup of 26 patients had precapillary pulmonary hypertension. Invasive haemodynamic and gas exchange parameters were measured at rest, 45° upright position, during exercise, after complete haemodynamic and respiratory recovery in lying position, and after rapid infusion of 500 mL isotonic solution. Most haemodynamic parameters increased at both exercise and intravenous fluid challenge, with the higher increase at exercise. Pulmonary vascular resistance decreased by -0.21 wood units at exercise and -0.56 wood units at intravenous fluid challenge (p = 0.3); 20% (10 of 49) of patients had an increase in pulmonary artery wedge pressure above the upper limit of 20 mmHg at exercise, and 20% above the respective limit of 18 mmHg after intravenous fluid challenge. However, only three patients exceeded the upper limit of pulmonary artery wedge pressure in both tests, i.e. seven patients only at exercise and seven other patients only after intravenous fluid challenge. In the subgroup of pulmonary hypertension patients, only two patients exceeded pulmonary artery wedge pressure limits in both tests, further five patients at exercise and four patients after intravenous fluid challenge. A sequential protocol in the same patient showed a significantly higher increase in haemodynamic parameters at exercise compared to intravenous fluid challenge. Both methods can unmask diastolic dysfunction at right heart catheter procedure, but in different patient groups.

Intravenous treprostinil via an implantable pump in pediatric pulmonary arterial hypertension.

Intravenous prostacyclin-based therapy improves survival in children with pulmonary arterial hypertension (PAH), but is typically administered via an external infusion pump, which places a considerable burden on the patient. Implanted pumps may overcome some of the limitations of external pumps. We describe the first long-term use of an implanted pump for intravenous treprostinil delivery in a pediatric patient with PAH. Our patient was experiencing marked dyspnea on exertion despite triple combination therapy with bosentan, sildenafil, and inhaled iloprost. Parenteral prostacyclin-based therapy was discussed and the patient rejected options involving external pumps; she finally chose intravenous treprostinil delivery via an implanted pump (LENUS Pro®; fixed flow rate; 20 ml reservoir). The patient underwent pump implantation in July 2012 (aged 14 years) under general anesthesia with no peri- or postoperative complications. She showed marked improvements in fatigue and dyspnea over the subsequent weeks, and her inhaled iloprost regimen was slowly decreased and stopped after six months. During follow-up, the pump showed an unexpected, progressive increase in flow rate that allowed a treprostinil dose of 170 ng/kg/min to be achieved, but at the cost of shortened intervals between refills. The pump was therefore replaced in August 2017 with a newer model with an adjustable flow rate (Siromedes®). A catheter dislocation was corrected under local anesthesia one week after the replacement surgery. The patient is currently receiving treprostinil 170 ng/kg/min with percutaneous refills every 12-13 days. Thus, implantable pumps might be a valuable alternative to external pumps for treprostinil infusion in pediatric PAH.

Subcutaneous implantation of a new intravenous pump system for prostacyclin treatment in patients with pulmonary arterial hypertension.

BACKGROUND: Intravenous prostacyclin treatment is a well recognized option in patients suffering from pulmonary arterial hypertension (PAH), and remains the gold standard of treatment. However, intravenous prostacyclin treatment involves several limitations, because the available battery-driven pump systems carry the risk of line infections, catheter-related embolisms, thrombosis, and delivery system malfunctions. CASE REPORT: We report for the first time, to the best of our knowledge, on the safe transition procedure from subcutaneous to intravenous treprostinil in a 74-year-old woman suffering from severe PAH (New York Heart Association functional class III), using a new implantable, gas-driven, intravenous pump device (LenusPro, Tricumed/OMT, Frittlingen, Germany). CONCLUSIONS: This implantable pump system may overcome the well-known limitations and risks of commonly used delivery systems, and thus may provide a new option for continuous intravenous prostacyclin treatment in patients with PAH.

Successful treatment of portopulmonary hypertension with the selective endothelin receptor antagonist Sitaxentan.

Portopulmonary hypertension (POPH) is a rare complication of portal hypertension. Prostanoids have been shown to be effective in the treatment of POPH and have been used as a bridge to liver transplantation. More recently, case series revealed beneficial effects of both the dual endothelin receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil. The efficacy of sitaxentan, a selective endothelin receptor A (ERA) antagonist in the reversal of POPH, is still unclear. We report a case of POPH that was successfully treated with oral sitaxentan. Haemodynamic and symptomatic improvements were maintained after a 12-week long-term treatment period. Additionally, hepatic vein pressure gradient significantly decreased from 12 mmHg to 8 mm after treatment with sitaxentan. This is the first reported case of a successful therapy with a selective ERA antagonist in a patient suffering from POPH. Oral sitaxentan therapy might be a promising new option for patients suffering from POPH.