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γ-glutamyl transferase (GGT), the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, and the neutrophil-to-lymphocyte ratio (NLR) are prognostic biomarkers in several cardiovascular diseases, but their relevance in pulmonary hypertension (PH) is not fully understood. We aimed to assess their prognostic value in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH).We retrospectively analyzed 731 incident patients with idiopathic PAH or CTEPH who entered the Giessen PH registry during 1993-2019. A risk stratification score based on GGT, AST/ALT ratio, and NLR tertiles was compared with a truncated version of the European Society of Cardiology/European Respiratory Society (ESC/ERS) risk stratification scheme. Associations with survival were evaluated using Kaplan-Meier and Cox regression analyses. External validation was performed in 311 patients with various types of PAH or CTEPH from a second German center.GGT levels, AST/ALT, and NLR independently predicted mortality at baseline and during follow-up. The scoring system based on these biomarkers predicted mortality at baseline and during follow-up (both log-rank p0.001; hazard ratio [95% confidence interval], high vs low risk: baseline, 7.6 [3.9, 15.0]; follow-up, 13.3 [4.8, 37.1]). Five-year survival of low, intermediate, and high risk groups was 92%, 76%, and 51%, respectively, at baseline and 95%, 78%, and 50%, respectively, during follow-up. Our scoring system showed characteristics comparable to the ESC/ERS scheme, and predicted mortality in the validation cohort.GGT, AST/ALT, and NLR were reliable prognostic biomarkers at baseline and during follow-up, with predictive power comparable to the gold standard for risk stratification.

We sought to explore whether classification of patients with heart failure and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) according to their left ventricular ejection fraction (LVEF) identifies differences in their exercise hemodynamic profile, and whether classification according to an index of right ventricular (RV) function improves differentiation. Patients with HFmrEF and HFpEF have hemodynamic compromise on exertion. The classification according to LVEF implies a key role of the left ventricle. However, RV involvement in exercise limitation is increasingly recognized. The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PASP) ratio is an index of RV and pulmonary vascular function. Whether exercise hemodynamics differ more between HFmrEF and HFpEF than between TAPSE/PASP tertiles is unknown. We analyzed 166 patients with HFpEF (LVEF ≥ 50%) or HFmrEF (LVEF 40–49%) who underwent basic diagnostics (laboratory testing, echocardiography at rest, and cardiopulmonary exercise testing [CPET]) and exercise with right heart catheterization. Hemodynamics were compared according to echocardiographic left ventricular or RV function. Exercise hemodynamics (e.g. pulmonary arterial wedge pressure/cardiac output [CO] slope, CO increase during exercise, and maximum total pulmonary resistance) showed no difference between HFpEF and HFmrEF, but significantly differed across TAPSE/PASP tertiles and were associated with CPET results. N-terminal pro-brain natriuretic peptide concentration also differed significantly across TAPSE/PASP tertiles but not between HFpEF and HFmrEF. In patients with HFpEF or HFmrEF, TAPSE/PASP emerged as a more appropriate stratification parameter than LVEF to predict clinically relevant impairment of exercise hemodynamics. Stratification of exercise hemodynamics in patients with HFpEF or HFmrEF according to LVEF or TAPSE/PASP, showing significant distinctions only with the RV-based strategy. All data are shown as median [upper limit of interquartile range] and were calculated using the independent-samples Mann–Whitney U test or Kruskal–Wallis test. PVR pulmonary vascular resistance; max maximum level during exercise.

Right ventricular (RV) function determines outcome in pulmonary arterial hypertension (PAH). RV pressure-volume loops, the gold standard for measuring RV function, are difficult to analyze. Our aim was to investigate whether simple assessments of RV pressure-volume loop morphology and RV systolic pressure differential reflect PAH severity and RV function. We analyzed multibeat RV pressure-volume loops (obtained by conductance catheterization with preload reduction) in 77 patients with PAH and 15 patients without pulmonary hypertension in two centers. Patients were categorized according to their pressure-volume loop shape (triangular, quadratic, trapezoid, or notched). RV systolic pressure differential was defined as end-systolic minus beginning-systolic pressure (ESP − BSP), augmentation index as ESP − BSP/pulse pressure, pulmonary arterial capacitance (PAC) as stroke volume/pulse pressure, and RV-arterial coupling as end-systolic/arterial elastance (Ees/Ea). Trapezoid and notched pressure-volume loops were associated with the highest afterload (Ea), augmentation index, pulmonary vascular resistance (PVR), mean pulmonary arterial pressure, stroke work, B-type natriuretic peptide, and the lowest Ees/Ea and PAC. Multivariate linear regression identified Ea, PVR, and stroke work as the main determinants of ESP − BSP. ESP − BSP also significantly correlated with multibeat Ees/Ea (Spearman’s ρ: −0.518, P < 0.001). A separate retrospective analysis of 113 patients with PAH showed that ESP − BSP obtained by routine right heart catheterization significantly correlated with a noninvasive surrogate of RV-arterial coupling (tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio; ρ: −0.376, P < 0.001). In conclusion, pressure-volume loop shape and RV systolic pressure differential predominately depend on afterload and PAH severity and reflect RV-arterial coupling in PAH.

The functional relevance of right atrial (RA) function in pulmonary hypertension (PH) remains incompletely understood. The purpose of this study was to explore the correlation of cardiac magnetic resonance (CMR) feature tracking-derived RA phasic function with invasively measured pressure-volume (P-V) loop-derived right ventricular (RV) end-diastolic elastance ( Eed) and RV-arterial coupling [ratio of end-systolic elastance to arterial elastance ( Ees/ Ea)]. In 54 patients with severe PH, CMR was performed within 24 h of diagnostic right heart catheterization and P-V measurements. RA phasic function was assessed by CMR imaging of RA reservoir, passive, and active strain. The association of RA phasic function with indexes of RV function was evaluated by Spearman’s rank correlation and linear regression analyses. Median [interquartile range] RA reservoir strain, passive strain, and active strain were 19.5% [11.0–24.5], 7.0% [4.0–12.0], and 13.0% [7.0–18.5], respectively. Ees/ Ea was 0.73 [0.48–1.08], and Eed was 0.14 mmHg/mL [0.05–0.22]. RV diastolic impairment [RV end-diastolic pressure (EDP) and Eed] was correlated with RA phasic function, but Ea and Ees were not. In addition, RA phasic function was correlated with inferior vena cava diameter. In multivariate linear regression analysis, adjusting for key P-V loop indexes, Eed and EDP remained significantly associated with RA phasic function. We conclude that RA phasic function is altered in relation to impaired diastolic function of the chronically overloaded right ventricle and contributes to backward venous flow and systemic congestion. These results call for more attention to RA function in the management of patients with PH. NEW & NOTEWORTHY There is growing awareness of the importance of the right atrial (RA)-right ventricular (RV) axis in pulmonary hypertension (PH). Our results uncover alterations in RA phasic function that are related to depressed RV lusitropic function and contribute to backward venous return and systemic congestion in chronic RV overload. Assessment of RA function should be part of the management and follow-up of patients with PH.

Background: Percutaneous mitral valve repair (PMVR) in high-risk patients is currently controversial, especially in those with secondary mitral regurgitation (MR). Exercise pulmonary hemodynamics may help to unmask cardiac dysfunction as well as the dynamic impact of MR. The present study sought to explore the clinical impact of preprocedural exercise right heart catheterization (RHC) for the selection of patients who could most benefit from PMVR. Methods: Sixty-eight patients with symptomatic primary and secondary MR and exercise RHC before PMVR were included in this retrospective analysis of the association of exercise RHC parameters with survival and improvement in New York Heart Association class within 12 months. Results: Median patient age was 77 years (±8.5), 37% were female, and 81% presented with New York Heart Association class III. A total of 65% of the patients had left ventricular ejection fraction P P Conclusions: In our cohort of patients with indication for PMVR, preprocedural exercise RHC was able to identify patients with an unfavorable outcome. Further studies with larger patient numbers are warranted before this approach can be implemented in a structured diagnostic workup of patients under evaluation for PMVR.

Aim: This study assessed the utility of osteopontin (OPN) and galectin-3 (Gal-3) as biomarkers of maladaptive right ventricular remodeling in pulmonary hypertension (PH). Materials & methods: We examined plasma levels of OPN and Gal-3 in patients with PH (n = 62), dilated cardiomyopathy (n = 34), left ventricular hypertrophy (LVH; n = 47), and controls without right ventricle (RV) or LV abnormalities (n = 38). Results: OPN and Gal-3 levels were higher in PH, dilated cardiomyopathy and LVH than in the controls. OPN concentrations in PH patients with maladaptive RV were significantly higher than in those with adaptive RV. Gal-3 did not differentiate between adaptive and maladaptive RV remodeling in PH. OPN and Gal-3 levels did not correlate with parameters of LV remodeling. Conclusion: OPN is a potential biomarker of RV maladaptation.

Right ventricular (RV) function is the main determinant of the outcome of patients with pulmonary hypertension (PH). RV dysfunction develops gradually and worsens progressively over the course of PH, resulting in RV failure and premature death. Currently, approved therapies for the treatment of left ventricular failure are not established for the RV. Furthermore, the direct effects of specific vasoactive drugs for treatment of pulmonary arterial hypertension (PAH, Group 1 of PH) on RV are not fully investigated. Pulmonary artery banding (PAB) allows to study the pathogenesis of RV failure solely, thereby testing potential therapies independently of pulmonary vascular changes. This review aims to discuss recent studies of the mechanisms of RV remodeling and RV-directed therapies based on the PAB model.

Acute respiratory distress syndrome (ARDS) is often associated with elevated levels of CO2 (hypercapnia) and impaired alveolar fluid clearance. Misfolding of the Na,K-ATPase (NKA), a key molecule i...

The purpose of this study was to assess the diagnostic accuracy of computed tomography pulmonary angiogram (CTPA) including dual energy and reconstruction of iodine maps for diagnosing CTEPH. This method for detecting embolisms and perfusion failures was compared with V/Q-SPECT. An additional purpose was to compare the applied radiation dose of both techniques. 71 patients (49 women) with suspected CTEPH were included in this prospective study. The patients received a V/Q-SPECT and a dual-energy CTPA. Iodine maps were reconstructed from the data set. CTPA and the iodine maps were read by an experienced radiologist unaware of the clinical information as well as the results of the V/Q-SPECT. Results were compared to the V/Q-SPECT. DLP and the applied amount of radionuclides (MAA, Technegas) were obtained for comparison of radiation dose. For the diagnosis of CTEPH, the sensitivity of DECT was 1.000, specificity 0.966, PPV 0.867 and NPV 1.000, respectively. There was not a considerable difference in the x-ray exposure between the DECT examination and the V/Q-SPECT (1.892 mSv vs. 1.911 mSv; p = 0.6115). Both examination modalities were highly consistent regarding the classification of pathological segments (1177/1278 segments, 92,09 %, κ = 0,5938). This study presents the DECT, in combination with reconstructed iodine maps, as a potential alternative to the current imaging technique of first choice, V/Q-SPECT. For creating future prospective diagnostic algorithms, the implementation of DECT screening with iodine maps should be considered.· DECT correctly identified all CTEPH patients.. · There is substantial agreement between DECT and V/Q-SPECT in the classification of pathological segments.. · There is no significant difference in radiation exposure during DECT examination and V/Q-SPECT examination.. · Reduced radiation dose does not negatively impact image quality..· Schüßler A, Richter M, Tello K et al. Evaluation der diagnostischen Genauigkeit und der Strahlendosis der Dual-Energy-Computertomografie (DECT) bei chronisch thromboembolischer pulmonaler Hypertonie (CTEPH). Fortschr Röntgenstr 2021; 193: 1318 - 1326.ZIEL: Ziel der Studie war es herauszufinden, wie exakt die diagnostische Genauigkeit der computertomografischen Pulmonalisangiografie (CTPA) unter Hinzunahme von Dual-Energy und Rekonstruktionen von Jodkarten bei der Diagnosestellung einer CTEPH ist. Zudem wurde die Übereinstimmung der CTPA mit der Ventilations-/Perfusionsszintigrafie (V/Q-SPECT) bei der Detektion von Embolien und Perfusionsausfällen untersucht. Ein weiteres Ziel war es, die applizierte Strahlenexposition beider Techniken miteinander zu vergleichen. 71 Patienten (49 Frauen) mit dem Verdacht auf eine CTEPH wurden in diese prospektive Studie eingeschlossen. Die Patienten erhielten eine V/Q-SPECT und eine Dual-Energy-CTPA und hieraus rekonstruierte Jodkarten. Die Analyse der CTPA und der Jodkarten erfolgte durch einen erfahrenen Radiologen, verblindet zu den klinischen Angaben und in Unkenntnis des V/Q-SPECT-Befundes. Die Ergebnisse wurden mit dem Befund der V/Q-SPECT verglichen. DLP und die applizierten Radionuklidmengen (MAA, Technegas) wurden zur Ermittlung der Strahlenexposition erfasst. Die DECT erzielte eine Sensitivität von 1,000, eine Spezifität von 0,966, einen PPV von 0,867 und einen NPV von 1,000. Zwischen den beiden Untersuchungsmodalitäten gab es, in Bezug auf die Strahlenexposition, nahezu keinen Unterschied (1,911 mSv vs. 1,892 mSv). Die Untersuchungsmodalitäten zeigten im Hinblick auf Perfusionsdefizite eine hohe Übereinstimmung (1177/1278 Segmente, 92,09 %; κ = 0,5938). Die DECT präsentierte sich, in Kombination mit den Jodkarten, als potenzielle Alternative zum gegenwärtigen bildgebenden Verfahren der ersten Wahl, der V/Q-SPECT. Bei der Erstellung zukünftiger diagnostischer CTEPH-Untersuchungsalgorithmen sollte die Implementierung der DECT erwogen werden. · Die DECT stufte alle CTEPH-Patienten als richtig positiv ein.. · Hohe Übereinstimmung zwischen DECT und V/Q-SPECT bei der Einteilung pathologischer Segmente.. · Strahlenexposition DECT-Untersuchung und V/Q SPECT kein signifikanter Unterschied.. · Trotz eingesparter Strahlendosis keine Einbußen der Bildqualität..· Schüßler A, Richter M, Tello K et al. Evaluation of Diagnostic Accuracy and X-Ray Exposure of Dual-Energy Computed Tomography (DECT) in the Course of Chronic Thromboembolic Pulmonary Hypertension (CTEPH). Fortschr Röntgenstr 2021; 193: 1318 – 1326.

This study sought to compare cardiac magnetic resonance (CMR) imaging-derived right ventricular (RV) strain and invasively measured pressure-volume loop-derived RV contractility, stiffness, and afterload and RV-arterial coupling in pulmonary hypertension (PH).In chronic RV pressure overload, RV-arterial uncoupling is considered the driving cause of RV maladaptation and eventual RV failure. The pathophysiological and clinical value of CMR-derived RV strain relative to that of invasive pressure-volume loop-derived measurements in PH remains incompletely understood.In 38 patients with PH, global RV CMR strain was measured within 24 h of diagnostic right heart catheterization and conductance (pressure-volume) catheterization. Associations were evaluated by correlation, multivariate logistic binary regression, and receiver operating characteristic analyses.Long-axis RV longitudinal and radial strain and short-axis RV radial and circumferential strain were -18.0 ± 7.0%, 28.9% [interquartile range (IQR): 17.4% to 46.6%]; 15.6 ± 6.2%; and -9.8 ± 3.5%, respectively. RV-arterial coupling (end-systolic [Eds]/arterial elastance [Ea]) was 0.76 (IQR: 0.47 to 1.07). Peak RV strain correlated with Ees/Ea, afterload (Ea), RV diastolic dysfunction (Tau), and stiffness (end-diastolic elastance [Eed]) but not with contractility (Ees). In multivariate analysis, long-axis RV radial strain was associated with RV-arterial uncoupling (Ees/Ea: 0.805; odds ratio [OR]: 5.50; 95% confidence interval [CI]: 1.50 to 20.18), whereas long-axis RV longitudinal strain was associated with increased RV diastolic stiffness (Eed: ≥0.124 mm Hg/ml; OR: 1.23; 95% CI: 1.10 to 1.51). The long-axis RV longitudinal strain-to-RV end-diastolic volume/body surface area ratio strongly predicted RV diastolic stiffness (area under receiver operating characteristic curve: 0.908).In chronic RV overload, CMR-determined RV strain is associated with RV-arterial uncoupling and RV end-diastolic stiffness and represents a promising noninvasive alternative to current invasive methods for assessment of RV-arterial coupling and end-diastolic stiffness in patients with PH. (Right Ventricular Haemodynamic Evaluation and Response to Treatment [Rightheart I]; NCT03403868).

The right ventricle (RV) is the main determinant of prognosis in pulmonary hypertension. Adaptation and maladaptation of the RV are of crucial importance. In the course of disease, RV contractility increases through changes in muscle properties and muscle hypertrophy. At a certain point, the point of "uncoupling," the afterload exceeds contractility, and maladaptation as well as dilation occurs to maintain stroke volume (SV). To understand the adaptational processes and to further develop targeted medication directly affecting load-independent contractility, an accurate and precise assessment of contractility and RV-pulmonary artery (PA) coupling should be performed. In this review, we shed light on existing methods to assess RV function, including the gold standard measurement of contractility and RV-PA coupling, and we evaluate existing surrogates of RV-PA coupling.

Background Currently an echocardiographic threshold for the tricuspid regurgitation gradient (TRG) of > 31 mmHg is recommended for screening for pulmonary hypertension (PH). Invasively diagnosed PH was recently redefined as mean pulmonary arterial pressure (mPAP) > 20 mmHg instead of ≥ 25 mmHg. We investigated the ability of TRG to screen for the new PH-definition. Methods Retrospective assessment of echocardiography and right heart catheterisation data from 1572 patients entering the Giessen PH-Registry during 2008–2018. Accuracy of different TRG thresholds and other echocardiographic parameters was evaluated using receiver operating characteristic curves. Findings 1264 patients fulfilled the new PH-definition. Positive (PPV) and negative predictive values and accuracy of TRG > 46 mmHg were 95%, 39%, and 73%, respectively, for the new PH-definition. Lowering the TRG cut-off to 31 mmHg and below worsened PPV to ≤ 89%. The PPV of TRG for pre-capillary PH (mPAP > 20 mmHg and pulmonary vascular resistance ≥ 3 Wood Units) was ≤ 85%. In patients with TRG ≤ 46 mmHg, tricuspid annular plane systolic excursion/TRG and TRG/right ventricular outflow tract acceleration time were superior to TRG in screening for newly defined pre-capillary PH. Interpretation In patients with suspected PH referred to a tertiary care centre, the PPV of TRG to meet the new PH-definition depended strongly on the TRG cut-off used. Our data do not support lowering the TRG cut-off. Combining TRG with other echocardiographic parameters might improve the validity of echocardiographic screening for PH.

Aims We sought to assess the feasibility of constructing right ventricular (RV) pressure–volume (PV) loops solely by echocardiography. Methods and results We performed RV conductance and pressure wire (PW) catheterization with simultaneous echocardiography in 35 patients with pulmonary hypertension. To generate echocardiographic PV loops, a reference RV pressure curve was constructed using pooled PW data from the first 20 patients (initial cohort). Individual pressure curves were then generated by adjusting the reference curve according to RV isovolumic and ejection phase duration and estimated RV systolic pressure. The pressure curves were synchronized with echocardiographic volume curves. We validated the reference curve in the remaining 15 patients (validation cohort). Methods were compared with correlation and Bland–Altman analysis. In the initial cohort, echocardiographic and conductance-derived PV loop parameters were significantly correlated {rho = 0.8053 [end-systolic elastance (Ees)], 0.8261 [Ees/arterial elastance (Ea)], and 0.697 (stroke work); all P Conclusion The novel echocardiographic method is an acceptable alternative to invasively measured PV loops to assess contractility, RV-arterial coupling, and RV myocardial work. Further validation is warranted.

Coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) is associated with high mortality. Lung-protective ventilation is the current standard of care in patients with ARDS, but it might lead to hypercapnia, which is independently associated with worse outcomes. Extracorporeal carbon dioxide removal (ECCO2R) has been proposed as an adjuvant therapy to avoid progression of clinical severity and limit further ventilator-induced lung injury, but its use in COVID-19 has not been described yet. Acute kidney injury requiring renal replacement therapy (RRT) is common among critically ill COVID-19 patients. In centers with available dialysis, low-flow ECCO2R (

In 301 treatment-naive patients with pulmonary arterial hypertension stratified by the European Society of Cardiology/European Respiratory Society risk score, further stratification of intermediate-risk patients based on six-minute walk distance and the tricuspid annular plane systolic excursion/systolic pulmonary artery pressure ratio identified a subset with mortality rates comparable to low-risk patients.

Introduction: Pulmonary hypertension guidelines recommend treatment decisions based on risk stratification. The suggested risk stratification scheme has been validated in several real-life PAH cohorts confirming its usefulness for risk adapted decision making at baseline as well as during follow-up. It is, however, unclear whether patients at intermediate risk should be treated as high risk patients or as low risk patients. We therefore aimed to investigate whether six-minute walk distance (SMWd) and TAPSE can divide intermediate risk patients into a low-intermediate and high-intermediate group. Methods: We retrospectively analyzed incident patients with PAH who entered the Giessen PH registry. Haemodynamic parameters, echocardiographic parameters, WHO functional class, SMWd and BNP were considered for risk stratification. Statistical analyses were done as appropriate using R (The R Foundation, Vienna, Austria) and SPSS (Version 26, IBM, Armonk, USA). Results: 302 PAH patients (58±15 years, 65% female) were included in the analysis. 5-year survival of patients at low (n=96), intermediate (n=180) and high risk (n=18) was 69%, 58% and 22%. Interestingly, stratifying intermediate-risk patients using SMWd and TAPSE allowed to distinguish between low-intermediate and high-intermediate patients (5-year survival 67% and 27%). Conclusion: 5-year survival did not differ significantly between low- and low-intermediate as well as high- and high-intermediate risk patients. Hence, risk stratification into four groups (low, low-intermediate, high-intermediate and high risk) using SMWd and TAPSE for focused stratification of intermediate risk patients is a straight-forward and simple tool for in-depth risk stratification in PAH.

The pulmonary physician must be aware of pulmonary toxicities if patients are treated with tyrosine kinase inhibitors. The compounds have different therapeutic targets and are associated to different extents with pulmonary complications.https://bit.ly/3gXUF8h

Pulmonary hypertension is frequently underdiagnosed, and referral is delayed with subsequent impact on outcomes. During the SARS-CoV-2 pandemic, restrictions on daily life and changes in hospitals' daily routine care were introduced in Germany. This multi-centre study provides evidence for a negative influence of these restrictions on patient care in pulmonary hypertension expert referral centres.

Right ventricular (RV) dyssynchrony has been related to outcome in pulmonary arterial hypertension. Prospectively, we performed echocardiography with measurement of right ventricular dyssynchrony and pressure–volume loop catheterization in 27 pulmonary arterial hypertension patients. Afterload and diastolic function emerged as determinates of wall stress, which results in dyssynchrony., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND The updated hemodynamic definition of pulmonary hypertension (PH) due to interstitial lung disease (ILD) differentiates severe and non-severe phenotypes, but no further risk stratification strategy has been established or validated for severe PH due to ILD. We aimed to assess the prognostic value of a truncated version of the European Society of Cardiology/European Respiratory Society (ESC/ERS) PH risk stratification scheme in severe PH due to ILD. METHODS We retrospectively analyzed 185 patients with severe PH (mean pulmonary artery pressure of ≥35 mm Hg or ≥25 mm Hg with cardiac index RESULTS During follow-up (median [interquartile range]: 19 [7–40] months), 146 events occurred. Using baseline data for risk stratification, 5-year transplant-free survival of low-, intermediate-, and high-risk groups was 43%, 15%, and 4%, respectively (log-rank p = 0.010; hazard ratio of high- vs low-risk group: 3.116 [95% CI: 1.428–6.800]). Using follow-up data (at 11 [6.0–32.5] months) for risk stratification, 5-year survival of low-, intermediate-, and high-risk groups was 22%, 3%, and 0%, respectively (log-rank p = 0.005). CONCLUSIONS The truncated ESC/ERS scheme was clinically useful and demonstrated prognostic relevance in severe PH due to ILD.

Implantable infusion pumps might improve the convenience and safety of intravenous treprostinil for pulmonary arterial hypertension. The LENUS Pro (R) pump (approved in Europe) has a fixed flow rate. Based on 126 pumps and 2853 refills, we retrospectively analyzed the actual flow rate from 09/2010 to 09/2018. A relevant flow rate variance is evident after three years; therefore, flow rate monitoring and dose adjustment are mandatory.

Despite the pandemic status of COVID-19, there is limited information about host risk factors and treatment beyond supportive care. Immunoglobulin G (IgG) could be a potential treatment target. Our aim was to determine the incidence of IgG deficiency and associated risk factors in a cohort of 62 critically ill patients with COVID-19 admitted to two German ICUs (72.6% male, median age: 61 yr). Thirteen (21.0%) of the patients displayed IgG deficiency (IgG < 7 g/L) at baseline (predominant for the IgG1, IgG2, and IgG4 subclasses). Patients who were IgG-deficient had worse measures of clinical disease severity than those with normal IgG levels (shorter duration from disease onset to ICU admission, lower ratio of [Formula: see text] to [Formula: see text], higher Sequential Organ Failure Assessment score, and higher levels of ferritin, neutrophil-to-lymphocyte ratio, and serum creatinine). Patients who were IgG-deficient were also more likely to have sustained lower levels of lymphocyte counts and higher levels of ferritin throughout the hospital stay. Furthermore, patients who were IgG-deficient compared with those with normal IgG levels displayed higher rates of acute kidney injury (76.9% vs. 26.5%; P = 0.001) and death (46.2% vs. 14.3%; P = 0.012), longer ICU [28 (6–48) vs. 12 (3–18) days; P = 0.012] and hospital length of stay [30 (22–50) vs. 18 (9–24) days; P = 0.004]. Univariable logistic regression showed increasing odds of 90-day overall mortality associated with IgG-deficiency (odds ratio 5.14, 95% confidence interval 1.3–19.9; P = 0.018). IgG deficiency might be common in patients with COVID-19 who are critically ill, and warrants investigation as both a marker of disease severity as well as a potential therapeutic target.

Aim: This study assessed the utility of SPARC-like protein 1 (SPARCL1) as a biomarker of maladaptive right ventricular (RV) function in patients with pulmonary hypertension (PH). Methods: In this prospective study, we examined SPARCL1 levels in 105 patients with adaptive (n = 34) and maladaptive RV (n = 32) pressure overload caused by PH, dilated cardiomyopathy (DCM, n = 18) with LVEF < 35% and preserved RV function and controls without LV or RV abnormalities (n = 21). Results: The median SPARCL1 concentration in patients with maladaptive RV function was higher than in those with adaptive RV function (p p p p p Conclusion: SPARCL1 shows potential as novel biomarker of RV pathological remodelling and is associated with RV maladaptation and ventriculoarterial uncoupling in PH.

The ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP) has recently been reported as an independent prognostic parameter in heart failure. The TAPSE/PASP ratio has not been evaluated in detail in patients with pulmonary arterial hypertension (PAH).We analyzed TAPSE/PASP in 290 patients with PAH entered into the Giessen Pulmonary Hypertension Registry between November 2003 and July 2014. The prognostic relevance of TAPSE/PASP was assessed with multivariate Cox regression models, adjusting for clinical covariates, echocardiographic parameters, or hemodynamics, and was confirmed by Kaplan-Meier analyses.When stratified by tertile of TAPSE/PASP (low:0.19 mm/mmHg; middle: 0.19-0.32 mm/mmHg; high:0.32 mm/mmHg), patients in the low tertile showed significantly compromised hemodynamic, functional, and echocardiographic status compared with patients in the middle and high tertiles. In all multivariate models, TAPSE/PASP remained independently associated with overall mortality: the hazard ratio (95% confidence interval) was 1.87 (1.35-2.59) when adjusting for clinical covariates (p .001), 5.21 (2.17-12.5) when adjusting for echocardiographic parameters (p .001), 1.92 (1.30-2.83) when adjusting for hemodynamics (p = .001), and 4.13 (2.02-8.48) when adjusting for a selection of previously identified independent echocardiographic and hemodynamic prognostic indicators (p .001). Kaplan-Meier analyses showed better overall survival in the middle and high tertiles versus the low tertile (log-rank p .001).The TAPSE/PASP ratio is a meaningful prognostic parameter in patients with PAH and is associated with hemodynamics and functional class.

With rising altitude the partial pressure of oxygen falls. This phenomenon leads to hypobaric hypoxia at high altitude. Since more than 140 million people permanently live at heights above 2500 m and more than 35 million travel to these heights each year, understanding the mechanisms resulting in acute or chronic maladaptation of the human body to these circumstances is crucial. This review summarizes current knowledge of the body’s acute response to these circumstances, possible complications and their treatment, and health care issues resulting from long-term exposure to high altitude. It furthermore describes the characteristic mechanisms of adaptation to life in hypobaric hypoxia expressed by the three major ethnic groups permanently dwelling at high altitude. We additionally summarize current knowledge regarding possible treatment options for hypoxia-induced pulmonary hypertension by reviewing in vitro, rodent, and human studies in this area of research.

SCOPUS: le.j, info:eu-repo/semantics/published

Haemodynamic measurements from right heart catheterisation (RHC) are used for diagnosis and risk stratification in pulmonary hypertension (PH) [1]. The risk stratification scheme implemented in the guidelines for pulmonary arterial hypertension (PAH) has been validated in real-life cohorts [1–5]. However, the timing of measurements during RHC is not specified. We aimed to investigate the influence of the timing of measurements on RHC parameters and the consequences for risk stratification and diagnosis. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Yogeswaran reports non-financial support from University of Giessen, during the conduct of the study. Conflict of interest: Dr. Richter reports grants from German Research Foundation, non-financial support from University of Giessen, during the conduct of the study; grants from United Therapeutics, grants and personal fees from Bayer, personal fees from Actelion, personal fees from Mundipharma, personal fees from Roche, personal fees from OMT, outside the submitted work. Conflict of interest: Dr. Sommer reports personal fees from Actelion, outside the submitted work. Conflict of interest: Dr. Ghofrani reports grants from German Research Foundation, non-financial support from University of Giessen, during the conduct of the study; personal fees from Bayer, personal fees from Actelion, personal fees from Pfizer, personal fees from Merck, personal fees from GSK, grants and personal fees from Novartis, grants and personal fees from Bayer HealthCare, grants and personal fees from Encysive/Pfizer, grants from Aires, grants from German Research Foundation, grants from Excellence Cluster Cardiopulmonary Research, grants from German Ministry for Education and Research, personal fees from Takeda, outside the submitted work. Conflict of interest: Dr. Seeger reports grants from German Research Foundation, non-financial support from University of Giessen, during the conduct of the study; personal fees from Pfizer, personal fees from Bayer Pharma AG, outside the submitted work. Conflict of interest: Dr. Gall reports grants from German Research Foundation, non-financial support from University of Giessen, during the conduct of the study; personal fees from Actelion, personal fees from AstraZeneca, personal fees from Bayer, personal fees from BMS, personal fees from GSK, personal fees from Janssen-Cilag, personal fees from Lilly, personal fees from MSD, personal fees from Novartis, personal fees from OMT, personal fees from Pfizer, personal fees from United Therapeutics, outside the submitted work. Conflict of interest: Dr. Tello reports grants from German Research Foundation, non-financial support from University of Giessen, during the conduct of the study; personal fees from Actelion, personal fees from Bayer, outside the submitted work.

Background: The ratios of tricuspid annular plane systolic excursion (TAPSE)/echocardiographically measured systolic pulmonary artery pressure (PASP), fractional area change/invasively measured mean pulmonary artery pressure, right ventricular (RV) area change/end-systolic area, TAPSE/pulmonary artery acceleration time, and stroke volume/end-systolic area have been proposed as surrogates of RV-arterial coupling. The relationship of these surrogates with the gold standard measure of RV-arterial coupling (invasive pressure-volume loop-derived end-systolic/arterial elastance [Ees/Ea] ratio) and RV diastolic stiffness (end-diastolic elastance) in pulmonary hypertension remains incompletely understood. We evaluated the relationship of these surrogates with invasive pressure-volume loop-derived Ees/Ea and end-diastolic elastance in pulmonary hypertension. Methods: We performed right heart echocardiography and cardiac magnetic resonance imaging 1 day before invasive measurement of pulmonary hemodynamics and single-beat RV pressure-volume loops in 52 patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. The relationships of the proposed surrogates with Ees/Ea and end-diastolic elastance were evaluated by Spearman correlation, multivariate logistic regression, and receiver operating characteristic analyses. Associations with prognosis were evaluated by Kaplan-Meier analysis. Results: TAPSE/PASP, fractional area change/mean pulmonary artery pressure, RV area change/end-systolic area, and stroke volume/end-systolic area but not TAPSE/pulmonary artery acceleration time were correlated with Ees/Ea and end-diastolic elastance. Of the surrogates, only TAPSE/PASP emerged as an independent predictor of Ees/Ea (multivariate odds ratio: 18.6; 95% CI, 0.8–96.1; P =0.08). In receiver operating characteristic analysis, a TAPSE/PASP cutoff of 0.31 mm/mm Hg (sensitivity: 87.5% and specificity: 75.9%) discriminated RV-arterial uncoupling (Ees/Ea Conclusions: Echocardiographically determined TAPSE/PASP is a straightforward noninvasive measure of RV-arterial coupling and is affected by RV diastolic stiffness in severe pulmonary hypertension. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03403868.

The Breelib™ nebulizer was designed to reduce iloprost inhalation times for patients with pulmonary arterial hypertension (PAH). In 30 patients with PAH, rapid inhalation of iloprost 2.5 µg using Breelib™ caused significant improvements in invasively measured afterload and cardiac index but not echocardiographic right ventricular strain during 30 min post-inhalation.

Adaptation of right ventricular (RV) function to increased afterload—known as RV–arterial coupling—is a key determinant of prognosis in pulmonary hypertension. However, measurement of RV–arterial coupling is a complex, invasive process involving analysis of the RV pressure–volume relationship during preload reduction over multiple cardiac cycles. Simplified methods have therefore been proposed, including echocardiographic and cardiac MRI approaches. This review describes the available methods for assessment of RV function and RV–arterial coupling and the effects of pharmacotherapy on these variables. Overall, pharmacotherapies for pulmonary hypertension have shown beneficial effects on various measures of RV function, but it is often unclear if these are direct RV effects or indirect results of afterload reduction. Studies of the effects of pharmacotherapies on RV–arterial coupling are limited and mostly restricted to experimental models. Simplified methods to assess RV–arterial coupling should be validated and incorporated into routine clinical follow-up and future clinical trials. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.

Cardiopulmonary exercise testing (CPET) is an important tool for assessing functional capacity and prognosis in pulmonary arterial hypertension (PAH). However, the associations of CPET parameters with the adaptation of right ventricular (RV) function to afterload remain incompletely understood.In this study, 37 patients with PAH (idiopathic in 31 cases) underwent single-beat pressure–volume loop measurements of RV end-systolic elastance (Ees), arterial elastance (Ea) and diastolic elastance (Eed). Pulmonary arterial stiffness was assessed by magnetic resonance imaging. The results were correlated to CPET variables. The predictive relevance of RV function parameters for clinically relevant ventilatory inefficiency, defined as minute ventilation/carbon dioxide production (V′E/V′CO2) slope >48, was evaluated using logistic regression analysis.The median (interquartile range) of the V′E/V′CO2 slope was 42 (32–52) and the V′E/V′CO2 nadir was 40 (31–44). The mean±sd of peak end-tidal carbon dioxide tension (PETCO2) was 23±8 mmHg. Ea, Eed and parameters reflecting pulmonary arterial stiffness (capacitance and distensibility) correlated with the V′E/V′CO2 slope, V′E/V′CO2 nadir, PETCO2 and peak oxygen pulse. RV Ees and RV–arterial coupling as assessed by the Ees/Ea ratio showed no correlations with CPET parameters. Ea (univariate OR 7.28, 95% CI 1.20–44.04) and Eed (univariate OR 2.21, 95% CI 0.93–5.26) were significantly associated with ventilatory inefficiency (pOur data suggest that impaired RV lusitropy and increased afterload are associated with ventilatory inefficiency in PAH.