Pulmonary Hypertension (PH) is characterized as a hemodynamic disorder defined by a mean pulmonary arterial pressure (mPAP) exceeding 20 mmHg at rest. Classification into distinct subtypes is guided by measurements of pulmonary arterial wedge pressure (PAWP) and pulmonary vascular resistance (PVR): Precapillary PH: PAWP ≤ 15 mmHg accompanied by PVR > 2 Wood Units (WU), isolated Postcapillary PH: PAWP > 15 mmHg with PVR ≤ 2 WU and combined Pre- and Postcapillary PH: PAWP > 15 mmHg with PVR > 2 WU.Exercise-Induced PH refers to a pathophysiological condition in which resting mPAP is within normal limits but exhibits an exaggerated rise during physical exertion. This is quantified by a slope of mPAP relative to cardiac output exceeding 3 mmHg per liter per minute between rest and activity.The foundational framework for the clinical classification of PH, comprising five principal groups, remains unchanged. Nevertheless, several updates have been introduced: Reintegration of long-term responders to calcium channel blockers as a distinct subset within idiopathic pulmonary arterial hypertension (IPAH), Inclusion of new subcategories under Group 2 PH, which encompasses PH associated with left heart disease and Revision of Group 3 PH to categorize patients based on underlying pulmonary pathology rather than solely functional impairment.Additionally, Mitomycin-C and Carfilzomib have been recognized as pharmacologic agents with a confirmed causal relationship to the development of pulmonary arterial hypertension (PAH) and have thus been added to the list of definitively associated drugs.

Pulmonary hypertension associated with chronic lung diseases (PH-CLD) is one of the most common but frequently underdiagnosed forms of pulmonary hypertension (PH). Its presence has been consistently associated with worse prognosis and reduced quality of life for affected patients. Recent epidemiological data highlight the heterogeneity of this patient population, demonstrating that both the underlying lung disease and the severity of PH are critical determinants of prognosis and therapeutic decisions. The 7th World Symposium on Pulmonary Hypertension (WSPH) emphasized the importance of systematic diagnostic approaches and detailed phenotyping of PH-CLD. While some studies have shown potential benefits of PH-targeted therapies, others - particularly in COPD - have reported adverse outcomes. This position statement by the PH-DACH working group summarizes the key recommendations of the 11th Task Force of the 7th WSPH, critically assesses the current evidence, and comments specifically on deviations from the original text. The aim is to contribute to the development of practical diagnostic and therapeutic algorithms for patients with PH-CLD.

Die pulmonale Hypertonie bei chronischen Lungenerkrankungen (PH-CLD) ist eine der häufigsten, jedoch häufig unterdiagnostizierten Formen der pulmonalen Hypertonie (PH). Ihr Auftreten verschlechtert nachweislich Prognose und Lebensqualität der betroffenen Patient*innen. Neue epidemiologische Daten betonen die Heterogenität dieser Patientengruppe und zeigen, dass sowohl die zugrunde liegende Lungenerkrankung als auch der Schweregrad der PH für Prognose und Therapie entscheidend sind. Der 7. Weltkongress für pulmonale Hypertonie (WSPH) hat daher die Bedeutung einer systematischen Diagnostik und differenzierten Phänotypisierung von PH-CLD unterstrichen. Während einzelne Studien einen potenziellen Nutzen PH-spezifischer Therapien zeigen, berichten andere, etwa bei COPD, auch von negativen Effekten. Die vorliegende Stellungnahme der PH-DACH-Arbeitsgruppe fasst die wesentlichen Empfehlungen der 11. Task Force des 7. WSPH zusammen, bewertet die Evidenzlage kritisch und kommentiert gezielt Abweichungen vom Originaltext. Ziel ist es, einen Beitrag zur Entwicklung praxisnaher Diagnose- und Therapiealgorithmen für PH-CLD-Patienten zu leisten.

Die pulmonale Hypertonie (PH) stellt einen hämodynamisch definierten pathologischen Zustand dar, welcher durch einen mittleren pulmonalarteriellen Druck (mPAP) > 20 mmHg charakterisiert ist. Die differenzialdiagnostische Zuordnung erfolgt anhand des pulmonalarteriellen Wedge-Drucks (PAWP) und des pulmonalen Gefäßwiderstands (PVR): präkapilläre PH: PAWP ≤ 15 mmHg bei gleichzeitig erhöhtem PVR > 2 Wood Units (WU), isolierte postkapilläre PH: PAWP > 15 mmHg, PVR ≤ 2 WU und kombinierte post- und präkapilläre PH: PAWP > 15 mmHg und PVR > 2 WU. Die belastungsinduzierte PH ist definiert als normwertiger mPAP in Ruhe, jedoch pathologischer Drucksteigerung unter körperlicher Belastung, definiert durch eine Steigung des mPAP relativ zum Herzzeitvolumen (HZV) von > 3 mmHg/L/min. Die etablierte klinische Klassifikation der PH bleibt in ihrer Grundstruktur mit 5 Hauptgruppen erhalten. Modifikationen beinhalten: Re-Etablierung der Subgruppe der Langzeitresponder auf Kalziumkanalblocker innerhalb der idiopathischen pulmonalarteriellen Hypertonie (IPAH), Erweiterung der Gruppe 2 durch zusätzliche Subkategorien bei PH infolge Linksherzerkrankungen und verfeinerte Untergliederung der Gruppe 3 auf Basis spezifischer pulmonaler Grunderkrankungen statt rein funktioneller Einschränkungen. Die Wirkstoffe Mitomycin-C und Carfilzomib wurden neu in die Liste der Pharmaka mit gesicherter Assoziation zur Entwicklung einer PAH aufgenommen.

BACKGROUND:We assessed the efficacy and safety of tadalafil, a phosphodiesterase type 5 inhibitor, in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension. METHODS:In the double-blind PASSION study (Phosphodiesterase-5 Inhibition in Patients With Heart Failure With Preserved Ejection Fraction and Combined Post- and Pre-Capillary Pulmonary Hypertension), patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension were randomized 1:1 to receive tadalafil at a target dose of 40 mg or placebo. The primary end point was the time to the first composite event of adjudicated heart failure hospitalization or all-cause death. Secondary end points included all-cause mortality and improvements in New York Heart Association functional class or ≥10% improvement in 6-minute walking distance from baseline. RESULTS:Initially targeting 372 patients, the study was terminated early because of disruption in study medication supply. At that point, 125 patients had been randomized (placebo: 63; tadalafil: 62,). Combined primary end-point events occurred in 20 patients (32%) assigned to placebo and 17 patients (27%) assigned to tadalafil (hazard ratio, 1.02 [95% CI, 0.52-2.01]; P=0.95). There was a possible signal of higher all-cause mortality in the tadalafil group (hazard ratio, 5.10 [95% CI, 1.10-23.69]; P=0.04). No significant between-group differences were observed in other secondary end points. Serious adverse events occurred in 29 participants (48%) in the tadalafil group and 35 (56%) in the placebo group. CONCLUSIONS:The PASSION trial, terminated prematurely due to study medication supply disruption, does not support tadalafil use in patients with heart failure with preserved ejection fraction and combined postcapillary and precapillary pulmonary hypertension, with potential safety concerns and no observed benefits in primary and secondary end points. REGISTRATION:URL: https://www.clinicaltrialsregister.eu/; Unique identifier: 2017-003688-37. URL: https://drks.de; Unique identifier: DRKS -DRKS00014595.

AbstractAimsIn pulmonary arterial hypertension (PAH), upfront combination therapy with ERA and PDE5i is associated with a reduction in morbidity and mortality events and improves standard haemodynamics, but data remain limited. Aims of this study were (i) to capture detailed haemodynamic effects of rapid sequential dual combination therapy in patients with newly diagnosed PAH; (ii) to monitor the impact of treatment initiation on clinical variables and patients' risk status, and (iii) to compare the treatment effect in patients with ‘classical PAH’ and ‘PAH with co‐morbidities’.MethodsFifty patients (median age 57 [42–71] years, 66% female) with newly diagnosed PAH (76% idiopathic) were treated with a PD5i/sGC‐S or ERA, followed by addition of the respective other drug class within 4 weeks. All patients underwent repeat right heart catheterization (RHC) during early follow‐up.ResultsAt early repeat RHC (7 ± 2 months), there were substantial reductions in mean pulmonary artery pressure (mPAP: 52.2 ± 13.5 to 39.0 ± 10.6 mmHg; −25.3%), and pulmonary vascular resistance (PVR: 12.1 ± 5.7 to 5.8 ± 3.1 WU; −52.1%), and an increase in cardiac index (2.1 ± 0.4 to 2.7 ± 0.7 mL/min/m2; +32.2%) (all P < 0.05). Haemodynamic improvements correlated with improved clinical parameters including 6‐min walking distance (336 ± 315 to 389 ± 120 m), NTproBNP levels (1.712 ± 2.024 to 506 ± 550 ng/L, both P < 0.05) and WHO‐FC at 12 months, resulting in improved risk status, and were found in patients with few (n = 37) or multiple cardiovascular co‐morbidities (BMI > 30 kg/m2, hypertension, diabetes, coronary artery disease [≥3]; n = 13), albeit baseline PVR in PAH patients with multiple co‐morbidities was lower (9.3 ± 4.4 vs. 13.1 ± 5.9 WU) and PVR reduction less pronounced compared with those with few co‐morbidities (−42.7% vs. −54.7%). However, comprehensive haemodynamic assessment considering further variables of prognostic relevance such as stroke volume index and pulmonary artery compliance showed similar improvements among the two groups (SVI: +50.0% vs. +49.2%; PAC: 91.7% vs. 100.0%). Finally, the 4‐strata risk assessment approach was better able to capture treatment response as compared with other approaches, particularly in patients with co‐morbidities.ConclusionsRapid sequential combination therapy with PDE5i/sGC‐S and ERA substantially ameliorates cardiopulmonary haemodynamics at early follow‐up in patients without, and to a lesser extent, with cardiovascular co‐morbidities. This occurs in line with improvements of clinical parameters and risk status.

BACKGROUND: While computed tomography pulmonary angiography (CTPA) is an integral part of the work-up in patients with suspected pulmonary hypertension (PH), there is no established CTPA-derived prognostic marker. We aimed to assess whether quantitative readouts of lung vessel morphology correlate with established prognostic indicators in PH.METHODS: We applied a fully-automatic in-house developed algorithm for segmentation of arteries and veins to determine lung vessel morphology in patients with precapillary PH who underwent right heart catheterization and CTPA between May 2016 and May 2019. Primary endpoint of this retrospective study was the calculation of receiver operating characteristics for identifying low and high mortality risk according to the 3-strata risk assessment model presented in the current guidelines.RESULTS: We analyzed 73 patients, median age 65 years (interquartile range (IQR): 54-76), female/male ratio 35/38, median mean pulmonary arterial pressure 37 mm Hg (IQR: 30-46), and found significant correlations with important prognostic factors in pulmonary arterial hypertension. N-terminal pro-brain natriuretic peptide, cardiac index, mixed venous oxygen saturation, and 6-minute walking distance were correlated with the ratio of the number of arteries over veins with vessel diameters of 6-10 mm (Spearman correlation coefficients p = 0.64, p < 0.001; p = -0.60, p < 0.001; p = -0.47, p = 0.005; p = -0.45, p = 0.001, respectively). This ratio predicted a low-and high-risk score with an area under the curve of 0.73 (95% confidence interval (CI): 0.56-0.90) and 0.86 (95% CI: 0.74-0.97), respectively.CONCLUSIONS: The ratio of the number of arteries over veins with diameters between 6 and 10 mm is significantly correlated with prognostic markers in pulmonary hypertension and predicts low and high mortality risk.

BACKGROUND: Among patients with pulmonary arterial hypertension (PAH), acute vasoreactivity testing during right heart catheterization may identify acute vasoresponders, for whom treatment with high-dose calcium channel blockers (CCBs) is recommended. However, long-term outcomes in the current era remain largely unknown. We sought to evaluate the implications of acute vasoreactivity response for long-term response to CCBs and other outcomes. METHODS: Patients diagnosed with PAH between January 1999 and December 2018 at 15 pulmonary hypertension centers were included and analyzed retrospectively. In accordance with current guidelines, acute vasoreactivity response was defined by a decrease of mean pulmonary artery pressure by ≥10 mm Hg to reach <40 mm Hg, without a decrease in cardiac output. Long-term response to CCBs was defined as alive with unchanged initial CCB therapy with or without other initial PAH therapy and World Health Organization functional class I/II and/or low European Society of Cardiology/European Respiratory Society risk status at 12 months after initiation of CCBs. Patients were followed for up to 5 years; clinical measures, outcome, and subsequent treatment patterns were captured. RESULTS: Of 3702 patients undergoing right heart catheterization for PAH diagnosis, 2051 had idiopathic, heritable, or drug-induced PAH, of whom 1904 (92.8%) underwent acute vasoreactivity testing. A total of 162 patients fulfilled acute vasoreactivity response criteria and received an initial CCB alone (n=123) or in combination with another PAH therapy (n=39). The median follow-up time was 60.0 months (interquartile range, 30.8–60.0), during which overall survival was 86.7%. At 12 months, 53.2% remained on CCB monotherapy, 14.7% on initial CCB plus another initial PAH therapy, and the remaining patients had the CCB withdrawn and/or PAH therapy added. CCB long-term response was found in 54.3% of patients. Five-year survival was 98.5% in long-term responders versus 73.0% in nonresponders. In addition to established vasodilator responder criteria, pulmonary artery compliance at acute vasoreactivity testing, low risk status and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels at early follow-up correlated with long-term response and predicted survival. CONCLUSIONS: Our data display heterogeneity within the group of vasoresponders, with a large subset failing to show a sustained satisfactory clinical response to CCBs. This highlights the necessity for comprehensive reassessment during early follow-up. The use of pulmonary artery compliance in addition to current measures may better identify those likely to have a good long-term response.

Patients with left heart disease (LHD) often display pulmonary hypertension (PH), which impacts morbidity and mortality. The pathophysiology of PH is complex and entails pulmonary congestion due to elevated left-sided filling pressures, pulmonary vasoconstriction as well as vascular remodeling. The recent ESC/ERS Guidelines on pulmonary hypertension updated the hemodynamic definitions of pulmonary hypertension in general, and the subclassification of post-capillary PH. This review summarizes recent advances in the diagnostic work-up and management strategies of PH associated with LHD. Specifically, we summarize revisited hemodynamic definitions and the characteristics of isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH). Furthermore, we review the current knowledge on the pathogenesis of PH-LHD, the prognostic relevance of hemodynamic parameters, and the management strategies, differentiating between treatment of the underlying left heart disease and therapies targeting the pulmonary circulation. The article emphasises the need for precise diagnostic work-up and individualized treatment strategies in patients with PH-LHD.

The recently published new European guidelines for diagnosis and treatment of pulmonary hypertension now offer the so far most extensive description of genetic testing and counselling for pulmonary arterial hypertension patients. In addition, the importance of a clinical screening of healthy mutation carriers is highlighted as well as the genetic testing of patients with a suspicion of pulmonary veno-occlusive disease. We frame the respective parts of the guidelines on genetic testing and counselling in the context of recent data and provide comments. Finally, we give an outlook on novel molecular approaches starting from Sotatercept, addressing ion channels and novel therapeutic developments.

Pulmonary hypertension (PH) is a common condition in patients with left heart disease (LHD) that is highly relevant for morbidity and mortality. While post-capillary in nature, the pathophysiology of PH in patients with LHD (heart failure/cardiomyopathy, valvular heart disease; other: congenital/acquired) is complex, and decisions about management strategies are challenging. Recently, the updated European Society of Cardiology/European Respiratory Society guidelines on the diagnosis and treatment of PH revisited hemodynamic definitions and the sub-classification of post-capillary PH, and provided numerous new recommendations on the diagnosis and management of PH associated with various types of LHD. Here, we review several novel aspects that focus on: (a) updated hemodynamic definitions, including the distinction between isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH); (b) the pathogenesis of PH-LHD, considering various components contributing to PH, such as pulmonary congestion, vasoconstriction, and vascular remodeling; (c) the prognostic relevance of PH and hemodynamic markers; (d) the diagnostic approach to PH-LHD; (e) management strategies in PH-LHD, distinguishing between targeting the underlying left heart condition, the pulmonary circulation, and/or impaired right ventricular function. In conclusion, precise clinical and hemodynamic characterization and detailed phenotyping are essential for prognostication and the management of patients with PH-LHD.

ZusammenfassungDie kürzlich erschienenen, neuen Leitlinien für pulmonale Hypertonie bieten den bisher ausführlichsten Einblick in die genetische Diagnostik und Beratung von PAH-Patient*innen. Aber auch der Stellenwert des klinischen Screenings von gesunden Anlageträger*innen wird hervorgehoben sowie der genetischen Testung bei Patient*innen mit dem Verdacht auf eine pulmonal veno-okklusive Erkrankung. Die jeweiligen Abschnitte der Leitlinien werden im Folgenden in die aktuelle Datenlage eingebettet und kommentiert. Abschließend geben wir einen Ausblick auf neue molekulare Ansätze von Sotatercept über Ionenkanäle bis hin zu neuen therapeutischen Ansatzpunkten.

Background: Computed tomography pulmonary angiography (CTPA) is an integral part of the work-up in patients with suspected pulmonary hypertension (PH). However, there is no established CTPA-derived prognostic marker. Aim: To assess whether quantitative readouts of lung vessel morphology correlate with established prognostic indicators. Methods: Patients with pre-capillary PH who underwent right heart catheterization and CTPA between May 2016 and May 2019 were enrolled in this retrospective study. Lung vessel morphology was determined with a fully-automatic in-house developed algorithm for segmentation of arteries and veins. Primary endpoint was the calculation of receiver operating characteristics for identifying low and high mortality risk according to the 3-strata risk assessment model presented in the current guidelines. Results: We analysed 73 patients, median age 65 years (IQR: 54-76), 48% women, median mean pulmonary arterial pressure 37 mmHg (IQR: 30-46), and found correlations with important prognostic factors in PAH. N-terminal pro-brain natriuretic peptide, cardiac index, mixed venous oxygen saturation and six-minute walking distance were correlated with the ratio of the number of arteries over veins with vessel diameters of 6-10 mm (Spearman correlation coefficients ρ=0.64, -0.60, -0.47 and -0.45, respectively; all p≤0.005). This ratio predicted low- and high-risk scores with an area under the curve of 0.73 (95% CI: 0.56-0.90) and 0.86 (95% CI: 0.74-0.97), respectively. Conclusion: The ratio of the number of arteries over veins with diameters between 6-10 mm is significantly correlated with prognostic markers in pre-capillary PH and predicts low and high mortality risk.

Tweetable abstract In patients with pulmonary hypertension, wearing face masks during the COVID-19 pandemic has significant impact on the 6-min walk distance, which should be considered for the interpretation of the risk status, and the overall evaluation of patients https://bit.ly/3sL8guX

Background Catalytic class IA PI 3-kinase isoform p110α is a crucial regulator of cellular proliferation and survival in numerous cell types. While p110α is critically involved in pathogenic vascular remodeling, its physiological role for vascular integrity under stress conditions has not been studied. We report a protective function of smooth muscle p110α against abdominal aortic aneurysm (AAA) formation. Methods & Results In mice lacking p110α in smooth muscle cells (sm-p110α -/- ), perfusion of the infrarenal aorta with porcine pancreatic elastase (PPE) yielded substantially enhanced AAA formation compared to wild type controls. This disease phenotype is partly attributable to a subtle preexisting vascular phenotype under basal conditions, as sm-p110α -/- mice displayed a smaller media area, deranged aortic wall structure (detached smooth muscle cells, increased apoptotic cell death), and a diminished functional responsiveness of aortic rings to vasodilators. Furthermore, p110α is also implicated in regenerative processes during AAA development: Whereas wild type mice showed increased media hypertrophy, neointima formation and proliferation upon PPE intervention, these vascular remodeling processes were diminished in sm-p110α -/- mice. Concomitantly, increased numbers of elastic fiber breaks and ECM degradation were detected in sm-p110α -/- aorta. Mechanistically, we found that lack of p110α expression impaired smooth muscle cell proliferation, expression of contractile marker genes and production of elastin fibers. This phenotype largely depended on reduced phosphorylation and inactivation of FOXO1, as specific FOXO1 inhibition fully rescued proliferation of p110α -/- smooth muscle cells, and knockdown of FOXO1 increased expression of calponin and elastin. Conclusions Smooth muscle p110α protects against AAA disease by maintaining aortic wall homoeostasis and promoting SMC proliferation to compensate for cell loss during AAA development. Our findings have potential implications for current approaches aimed at p110α inhibition for cancer therapy and suggest new pharmacological strategies to activate p110α signaling in AAA disease.

Abstract Aims Guideline recommendations highlight the critical role of combination therapy for the treatment of pulmonary arterial hypertension (PAH). Conversely, registry data demonstrate that a considerable number of PAH patients remain on monotherapy. The reasons for this discrepancy remain elusive. The aim of this study was to assess the patient profiles, treatment patterns, and disease characteristics of patients diagnosed with PAH who were kept on monotherapy at experienced pulmonary hypertension (PH) centres and to capture potential reasons for monotherapy. Methods and results We analysed the patient profiles of 182 patients on monotherapy with PAH‐targeted drugs, managed at experienced PH expert centres (Cologne, Giessen, Heidelberg, and Dresden). Patients were identified based on their latest follow‐up visit and analysed retrospectively from the time of PAH diagnosis to last follow‐up. Patients were dichotomized by age, and patient characteristics, treatment patterns, response to therapy, change in risk status, and drug tolerability were recorded during the course of their disease. Patients' mean age was 69.1 ± 13.1 years at the most recent follow‐up (Key Time Point 1) and 64.5 ± 14.9 years at the time of diagnosis (Key Time Point 2). The mean time on monotherapy was 60.7 ± 53.8 months; 35.7/64.3% of patients were male/female. The majority (66.5%) had idiopathic PAH, followed by PAH associated with connective tissue disease (17.0%) and portopulmonary PH (8.2%). Among patients on monotherapy, there were five main clusters: (i) patients with failed escalation attempts mostly because of intolerability (26.9%); (ii) low risk on monotherapy, favourable response, and no reason for escalation (24.2%); (iii) patients with mild PAH (36.3%); (iv) elderly patients with PAH and multiple co‐morbidities (38.5%); and (v) patients with associated forms of PAH where the level of evidence for combination therapies is considered low (16.5%). There were substantial differences between patients above or below the median age (68 years). The most frequently used monotherapy for PAH was phosphodiesterase type 5 inhibitors (75.3%). Conclusions A considerable number of PAH patients are on monotherapy at large PH expert centres, characterized by specific reasons that justify this kind of treatment. Nevertheless, as comprehensive treatment strategies have shown improved long‐term outcomes even in mildly symptomatic patients, each case of monotherapy should be justified.

AbstractBackgroundPulmonary arterial hypertension (PAH) is a progressive disease with limited survival. Iron deficiency (ID) correlates with disease severity and mortality. While oral iron supplementation was shown to be insufficient in such patients, the potential impact of parenteral iron on clinical measures warrants further investigation.MethodsWe retrospectively analysed the long‐term effects of intravenous ferric carboxymaltose (FCM) on iron status and clinical measures in patients with PAH and ID [ferritin < 100 μg/L or ferritin 100–300 μg/L and transferrin saturation (TSAT) < 20%] who were on stable targeted PAH therapy, compared with matched controls without ID. Patients with ID received a single infusion of FCM (500 to 1000 mg). Clinical measures monitored included exercise capacity, World Health Organization (WHO) functional class, ESC/ERS risk status, and hospitalizations. The observation period was up to 18 months.ResultsOne hundred and seventeen patients (mean age 60.9 ± 16.1 years; 64.1% females) with confirmed PAH and on stable targeted therapy for ≥3 months were included (58 with and 59 patients without ID who did not receive FCM). In patients with ID, iron supplementation with FCM resulted in an immediate and sustained improvement of iron status for up to 18 months (serum iron, ferritin, TSAT, all P < 0.01). Fourteen patients in the FCM group received a second FCM infusion after 9.6 ± 4.8 months due to recurrent ID. At 6 and 18 months after FCM infusion, 6 min walk distance improved from 377.5 ± 15.9 at baseline to 412.5 ± 15.1 and 400.8 ± 14.5 m, respectively (both P < 0.05). WHO functional class (P < 0.05) and ESC/ERS risk status also improved, and there was a reduction of hospitalizations for worsening PAH in the 12 months post vs. prior to iron repletion (P = 0.029). No significant changes were observed in the control group. FCM was well tolerated in all patients, with no severe adverse events.ConclusionsIn addition to targeted therapy, correction of ID by parenteral iron supplementation with FCM appears feasible and safe, has sustained effects on iron status, and may improve the clinical status and hospitalization rates in patients with PAH. Larger controlled studies are required to confirm this finding.

Purpose of review Pulmonary hypertension is a common phenomenon in heart failure patients that is highly relevant for morbidity and outcome. Although postcapillary in nature, the pathophysiology of pulmonary hypertension in patients with heart failure with reduced or preserved ejection fraction is complex, and decisions about management strategies remain challenging. Recent findings Recently, the hemodynamic definitions and subclassification of postcapillary pulmonary hypertension have been revisited. The distinction between isolated postcapillary pulmonary hypertension (IpcPH) and combined post and precapillary pulmonary hypertension (CpcPH) and their definition are essential. Novel data on the prognostic impact of hemodynamic variables and right ventricular function highlight the importance of cardiopulmonary interaction in patients with left-sided heart failure (LHF). Furthermore, the impact of management strategies including medical therapy, remote hemodynamic monitoring, and interventional approaches on hemodynamics and outcome has recently been investigated. Here, we critically review recent developments and future considerations in this field, and highlight distinct treatment strategies targeting the underlying left heart condition, the pulmonary circulation, and/or impaired right ventricular function. Summary Detailed hemodynamic characterization and proper phenotyping are essential for prognostication and the management of patients with pulmonary hypertension associated with LHF, both in clinical practice and when addressing research questions.