RESUMEN
Pulmonary hypertension (PH) is a frequent hemodynamic condition that is highly prevalent in patients with heart failure and reduced (HFrEF) or preserved ejection fraction (HFpEF). Irrespective of left ventricular EF, the presence of PH and right ventricular (RV) dysfunction are highly relevant for morbidity and mortality in patients with heart failure. While elevated left-sided filling pressures and functional mitral regurgitation primarily lead to post-capillary PH, current guidelines and recommendations distinguish between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH), the latter being defined by a pulmonary vascular resistance (PVR) of ≥3 Wood units. Here, we describe the pathophysiology and clinical relevance of these distinct entities, and report on the diagnostic work-up including remote pulmonary artery pressure (PAP) monitoring. Furthermore, we highlight strategies to manage PH and improve RV function in heart failure, which may include optimized management of HFrEF and HFpEF (medical and interventional), sufficient volume control, catheter-based mitral valve repair, and-in selected cases-targeted PH therapy. In this context, we also highlight gaps in evidence and the need for further research.
Asunto(s)
Insuficiencia Cardíaca , Hipertensión Pulmonar , Insuficiencia Cardíaca/complicaciones , Humanos , Hipertensión Pulmonar/complicaciones , Pronóstico , Volumen Sistólico , Función Ventricular DerechaRESUMEN
AIM: To evaluate the feasibility of two-dimensional parametric parenchymal blood flow (2D-PPBF) to quantify perfusion changes in the lung parenchyma following balloon pulmonary angioplasty (BPA) for treatment of chronic thromboembolic pulmonary hypertension. MATERIALS AND METHODS: Overall, 35 consecutive interventions in 18 patients with 98 treated pulmonary arteries were included. To quantify changes in pulmonary blood flow using 2D-PPBF, the acquired digital subtraction angiography (DSA) series were post-processed using dedicated software. A reference region of interest (ROI; arterial inflow) in the treated pulmonary artery and a distal target ROI, including the whole lung parenchyma distal to the targeted stenosis, were placed in corresponding areas on DSA pre- and post-BPA. Half-peak density (HPD), wash-in rate (WIR), arrival to peak (AP), area under the curve (AUC), and mean transit time (MTT) were assessed. The ratios of the reference ROI to the target ROI (HPDparenchyma/HPDinflow, WIRparenchyma/WIRinflow; APparenchyma/APinflow, AUCparenchyma/AUCinflow, MTTparenchyma/MTTinflow) were calculated. The relative differences of the 2D-PPBF parameters were correlated to changes in the pulmonary flow grade score. RESULTS: The pulmonary flow grade score improved significantly after BPA (1 versus 3; p<0.0001). Likewise, the mean HPDparenchyma/HPDinflow (-10.2%; p<0.0001), APparenchyma/APinflow (-24.4%; p=0.0007), and MTTparenchyma/MTTinflow (-3.5%; p=0.0449) decreased significantly, whereas WIRparenchyma/WIRinflow (+82.4%) and AUCparenchyma/AUCinflow (+58.6%) showed a significant increase (p<0.0001). Furthermore, a significant correlation between changes of the pulmonary flow grade score and changes of HPDparenchyma/HPDinflow (ρ=-0.21, p=0.04), WIRparenchyma/WIRinflow (ρ=0.43, p<0.0001), APparenchyma/APinflow (ρ=-0.22, p=0.03), AUCparenchyma/AUCinflow (ρ=0.48, p<0.0001), and MTTparenchyma/MTTinflow (ρ=-0.39, p<0.0001) could be observed. CONCLUSION: The 2D-PPBF technique is feasible for the quantification of perfusion changes following BPA and has the potential to improve monitoring of BPA.
Asunto(s)
Angiografía de Substracción Digital/métodos , Angioplastia de Balón/métodos , Hipertensión Pulmonar/diagnóstico por imagen , Hipertensión Pulmonar/terapia , Interpretación de Imagen Asistida por Computador/métodos , Anciano , Algoritmos , Enfermedad Crónica , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Sepsis is defined as a systemic inflammatory response of the body to an infection. Besides anti-infective drugs and removal of the site of infection, no specific therapeutics that target the overwhelming host response are available. Clinical researchers are currently evaluating the extracorporeal elimination of circulating cytokines. Modern adsorbing techniques have increasingly been used for this purpose allowing an unselective but highly effective removal of the vast majority of circulating cytokines but also fail to replace used protective factors in patients' plasma. Therapeutic plasma exchange (TPE) however might represent a novel method to remove pathologically elevated cytokines and simultaneously to replace protective plasmatic factors. Here we report the case of a septic shock patient treated with TPE and review the available literature with respect to TPE as an adjunctive therapy in sepsis.
Asunto(s)
Intercambio Plasmático/métodos , Choque Séptico/terapia , Antibacterianos/uso terapéutico , Cuidados Críticos/métodos , Citocinas/sangre , Farmacorresistencia Bacteriana Múltiple , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/terapia , Humanos , Mediadores de Inflamación/sangre , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Norepinefrina/administración & dosificación , Norepinefrina/sangre , Plasmaféresis/métodos , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/terapia , Choque Séptico/inmunología , Infecciones Urinarias/inmunología , Infecciones Urinarias/terapia , Signos VitalesRESUMEN
The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. 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 risk stratification and follow-up assessment of patients with PAH. This manuscript summarizes the results and recommendations of this working group.
Asunto(s)
Determinación de la Presión Sanguínea/normas , Cardiología/normas , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Guías de Práctica Clínica como Asunto , Neumología/normas , Alemania , Humanos , Hipertensión Pulmonar/clasificación , Pronóstico , Medición de Riesgo/normas , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Antihipertensivos/administración & dosificación , Cardiología/normas , Hipertensión Pulmonar/terapia , Terapia Molecular Dirigida/normas , Guías de Práctica Clínica como Asunto , Neumología/normas , Alemania , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/genética , Técnicas de Diagnóstico Molecular/normasRESUMEN
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 management of decompensated right heart failure, intensive care management and perioperative management in patients with pulmonary hypertension. This article summarizes the results and recommendations of the working group on decompensated right heart failure, intensive care and perioperative management in patients with pulmonary hypertension.
Asunto(s)
Cardiología/normas , Hipertensión Pulmonar/cirugía , Monitoreo Intraoperatorio/normas , Guías de Práctica Clínica como Asunto , Neumología/normas , Disfunción Ventricular Derecha/prevención & control , Alemania , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico , Disfunción Ventricular Derecha/diagnóstico , Disfunción Ventricular Derecha/etiologíaRESUMEN
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.
Asunto(s)
Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/terapia , Lesión Pulmonar/complicaciones , Lesión Pulmonar/terapia , Guías de Práctica Clínica como Asunto , Neumología/normas , Cardiología/normas , Alemania , Humanos , Hipertensión Pulmonar/diagnóstico , Lesión Pulmonar/diagnósticoRESUMEN
The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH), but also other significant subgroups of pulmonary hypertension (PH). 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 chronic thromboembolic pulmonary hypertension (CTEPH). In every patient with PH of unknown cause CTEPH should be excluded. The primary treatment option is surgical pulmonary endarterectomy (PEA) in a specialized multidisciplinary CTEPH center. Inoperable patients or patients with persistent or recurrent CTEPH after PEA are candidates for targeted drug therapy. For balloon pulmonary angioplasty (BPA), there is currently only limited experience. This option - as PEA - is reserved to specialized centers with expertise for this treatment method. In addition, a brief overview is given on pulmonary artery sarcoma, since its surgical treatment is often analogous to PEA. The recommendations of this working group are summarized in the present paper.
Asunto(s)
Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/terapia , Guías de Práctica Clínica como Asunto , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Neumología/normas , Antihipertensivos/administración & dosificación , Cardiología/normas , Quimioterapia Combinada/normas , Fibrinolíticos/administración & dosificación , Humanos , Hipertensión Pulmonar/etiología , Terapia Molecular Dirigida/normas , Embolia Pulmonar/complicacionesRESUMEN
Extracorporeal membrane oxygenation (ECMO) is a special form of a miniaturized heart-lung machine with the ultimate goal to stabilize critically ill patients. Dependent on the cannulation strategy ECMO can support or replace heart and/or lung function. Medical indications and contraindications have to be evaluated thoroughly before cannulation. Moreover, before ECMO initiation a solid treatment aim has to be defined: bridge to recovery, bridge to decision, bridge to transplantation, and bridge to destination (i. e. implantation of a permanent assist device). Regarding invasiveness of the system, potential life-threatening complications, requirement of standardized monitoring of the patient and the device as well as tertiary care infrastructure, ECMO should exclusively be used in highly experienced tertiary centers.
Asunto(s)
Enfermedad Crítica/terapia , Vías Clínicas/organización & administración , Oxigenación por Membrana Extracorpórea/métodos , Oxigenación por Membrana Extracorpórea/tendencias , Medicina Basada en la Evidencia , Humanos , Selección de Paciente , Resultado del TratamientoRESUMEN
This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.
Asunto(s)
Oxigenación por Membrana Extracorpórea/mortalidad , Enfermedades Pulmonares/mortalidad , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/mortalidad , Respiración Artificial/mortalidad , Adolescente , Adulto , Niño , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Mortalidad Hospitalaria/tendencias , Humanos , Incidencia , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Factores de TiempoRESUMEN
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.
Asunto(s)
Guanilato Ciclasa/metabolismo , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/metabolismo , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/metabolismo , Pirazoles/administración & dosificación , Pirimidinas/administración & dosificación , Receptores Citoplasmáticos y Nucleares/metabolismo , Antihipertensivos/administración & dosificación , Enfermedad Crónica , Fibrinolíticos/administración & dosificación , Humanos , Hipertensión Pulmonar/complicaciones , Embolia Pulmonar/complicaciones , Pirazoles/farmacocinética , Pirimidinas/farmacocinética , Receptores Citoplasmáticos y Nucleares/agonistas , Guanilil Ciclasa Soluble , Resultado del TratamientoAsunto(s)
Hipertensión Pulmonar/terapia , Terapia Combinada , Conducta Cooperativa , Progresión de la Enfermedad , Femenino , Alemania , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/fisiopatología , Comunicación Interdisciplinaria , Cuidados Paliativos , Guías de Práctica Clínica como Asunto , Embarazo , Complicaciones Cardiovasculares del Embarazo/terapia , Centros de Atención TerciariaAsunto(s)
Conducta Cooperativa , Hipertensión Pulmonar/tratamiento farmacológico , Comunicación Interdisciplinaria , Terapia Molecular Dirigida/métodos , Adulto , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Terapia Combinada , Aprobación de Drogas , Quimioterapia Combinada , Antagonistas de los Receptores de Endotelina/efectos adversos , Antagonistas de los Receptores de Endotelina/uso terapéutico , Medicina Basada en la Evidencia , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/mortalidad , Inhibidores de Fosfodiesterasa 5/efectos adversos , Inhibidores de Fosfodiesterasa 5/uso terapéutico , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de Supervivencia , Resultado del TratamientoAsunto(s)
Benzamidas/uso terapéutico , Hipertensión Pulmonar/tratamiento farmacológico , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Benzamidas/efectos adversos , Alemania , Humanos , Hipertensión Pulmonar/mortalidad , Mesilato de Imatinib , Uso Fuera de lo Indicado , Piperazinas/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de Supervivencia , Disfunción Ventricular Derecha/tratamiento farmacológico , Disfunción Ventricular Derecha/mortalidadRESUMEN
Idiopathic pulmonary fibrosis (IPF), a manifestation of chronic progressive fibrosing interstitial pneumonia, is with a prevalence of 2-29 cases per 100,000 individuals a rare disease. Current treatment options are limited, and the mean survival time of the newly diagnosed (mostly elderly) patients is only about 2-3 years. As in Europe data are limited on the characteristics and management of such patients, INSIGHTS-IPF was initiated as a new registry that documents incident and prevalent patients with confirmed IPF diagnosis prospectively. Detailed data on patient characteristics, diagnostics, management, clinical outcomes, quality of life and resource utilization are recorded. It is planned to document 500 patients in 30 centers. The registry will contribute to the optimization of the management of IPF patients in the long term.
Asunto(s)
Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/terapia , Sistema de Registros , Adulto , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/uso terapéutico , Biopsia , Comparación Transcultural , Estudios Transversales , Femenino , Alemania , Humanos , Fibrosis Pulmonar Idiopática/mortalidad , Fibrosis Pulmonar Idiopática/patología , Pulmón/patología , Masculino , Pronóstico , Estudios Prospectivos , Piridonas/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Enfermedades Raras , Factores Sexuales , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Right-sided heart failure is a severe and often life-threatening complication of chronic pulmonary hypertension. The detection of trigger factors that induce right heart failure in previously stable patients is important to initiate a causal therapeutic strategy. Pulmonary embolism (PE) is a frequent cause of acute right heart failure and therapeutic strategies for PE are well documented in the current guidelines. Treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH) is surgical pulmonary endarterectomy (PEA) and patients with possible CTEPH should be referred to an experienced PEA surgeon without delay. Intensive care management for overt right heart failure is complex and includes the use of pulmonary vasodilators, individual adjustment of diuretic or volume therapy, augmentation of myocardial contractility and left ventricular afterload. Therapeutic regimens aim at optimized filling of the right ventricle, improvement of myocardial perfusion by avoiding tachycardia, elevating systemic pressure and reducing right ventricular afterload. Early communication with a specialized center for pulmonary hypertension is recommended.
Asunto(s)
Cuidados Críticos/métodos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Hipertensión Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Insuficiencia Cardíaca/etiología , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/terapia , Embolia Pulmonar/complicaciones , Resultado del TratamientoRESUMEN
In pulmonary hypertension there is a discrepancy between the dramatic but unspecific clinical presentation and the remodeling of mostly only limited segments of the vascular compartment of pulmonary parenchyma. Clinical diagnosis relies for the most part on invasive procedures, such as right heart catheterization. Therefore, morphology can provide a reliable etiopathogenetic classification only in close cooperation with the clinical partner disciplines involved. Moreover, the histopathological approach requires intimate knowledge of the vascular anatomy of the lungs and assessment of the parenchyma to be able to diagnose pulmonary hypertension and differentiate between the various types.
Asunto(s)
Hipertensión Pulmonar/patología , Pulmón/patología , Arteria Pulmonar/patología , Venas Pulmonares/patología , Cateterismo Cardíaco , Proliferación Celular , Endotelio Vascular/patología , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Enfermedades Pulmonares/patología , Músculo Liso Vascular/patología , Enfermedad Veno-Oclusiva Pulmonar/patología , Presión Esfenoidal Pulmonar/fisiologíaRESUMEN
Current guidelines for the treatment of patients with idiopathic pulmonary arterial hypertension (IPAH) recommend basing therapeutic decision-making on haemodynamic, functional and biochemical variables. Most of these parameters have been evaluated as risk predictors at the time of diagnosis. The aim of the present study was to assess the prognostic impact of changes in these parameters after initiation of targeted therapy. A cohort of 109 patients with IPAH who had undergone haemodynamic, functional and biochemical assessments at baseline and 3-12 months after initiation of pulmonary arterial hypertension (PAH)-targeted therapy, were followed for a median 38 months in order to determine predictors of mortality at baseline and during the course of their disease. Within the observation period, 53 (48.6%) patients died and four (3.7%) underwent lung transplantation. Kaplan-Meier estimates for transplantation-free survival were 92%, 67%, and 51% at 1, 3, and 5 yrs, respectively. Among baseline variables, 6-min walk distance, right atrial pressure, cardiac index, mixed-venous oxygen saturation (S(v,O(2))) and N-terminal-pro brain natriuretic peptide (NT-proBNP) were independent predictors of survival. During follow-up, changes in World Health Organization functional class, cardiac index, S(v,O(2)) and NT-proBNP proved significant predictors of outcome. When assigned to prognostic groups, improvements as well as deteriorations in these parameters after initiation of PAH-targeted therapy had a strong impact on survival. Measurements obtained at follow-up had a higher predictive value than variables obtained at baseline. Changes in established predictors of outcome during the course of the disease provide important prognostic information in patients with IPAH.