Publications by authors named "Manuel J Richter"

58 Publications

Exercise Hemodynamic Profiling Is Associated With Outcome in Patients Undergoing Percutaneous Mitral Valve Repair.

Circ Cardiovasc Interv 2021 Aug 11:CIRCINTERVENTIONS120010453. Epub 2021 Aug 11.

Department of Cardiology, Kerckhoff-Klinik, Bad Nauheim, Germany. (A.J.R., S.D.K., E.W., U.F.-R., V.M., C.W.H., C.L., C.W.).

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 <55%. MR was severe in 49% and moderate-to-severe in 51%. Twenty-two patients (32%) died within the follow-up period of 19 months (interquartile range, 9-32); they had a lower rise (Δ) in the V-wave on pulmonary artery wedge pressure tracings. Patients with ΔV-wave ≥17 mm Hg had a reduced risk of death after PMVR (hazard ratio, 0.11 [95% CI, 0.04-0.33], <0.001), independent of age, frailty index, and workload during RHC. A higher ΔV-wave was also associated with New York Heart Association improvement (odds ratio, 1.14 [95% CI, 1.07-1.24]; <0.001), and 79% of patients with ∆V-wave ≥15 mm Hg were in New York Heart Association class I or II at follow-up (<15 mm Hg: 28%). These results were for the most part confirmed in the subgroup of patients with secondary MR (65%).

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.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.010453DOI Listing
August 2021

Acute Impact of Prone Positioning on the Right Ventricle in COVID-19-Associated Acute Respiratory Distress Syndrome.

Circ Heart Fail 2021 08 30;14(8):e008810. Epub 2021 Jul 30.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center, Germany.

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.008810DOI Listing
August 2021

Osteopontin and galectin-3 as biomarkers of maladaptive right ventricular remodeling in pulmonary hypertension.

Biomark Med 2021 Aug 22;15(12):1021-1034. Epub 2021 Jul 22.

Department of Cardiology & Angiology, University of Giessen, Giessen, 35392, Germany.

This study assessed the utility of osteopontin (OPN) and galectin-3 (Gal-3) as biomarkers of maladaptive right ventricular remodeling in pulmonary hypertension (PH). 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). 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. OPN is a potential biomarker of RV maladaptation.
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http://dx.doi.org/10.2217/bmm-2021-0009DOI Listing
August 2021

Impact of SARS-CoV-2-Pandemic on Mental Disorders and Quality of Life in Patients With Pulmonary Arterial Hypertension.

Front Psychiatry 2021 24;12:668647. Epub 2021 Jun 24.

Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany.

Covid-19 pandemic may affect mental health and quality of life (QoL) in patients with pulmonary arterial hypertension (PAH). We assessed changes in anxiety and depression, quality of life (QoL) and self-described impact of Covid-19 in patients with PAH during the Covid-19 pandemic. This study included 152 patients with PAH from two German referral centers. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS-A and HADS-D) at two different timepoints before and during the Covid-19 pandemic with a median of 232 days between baseline and follow-up. QoL was assessed using EQ-5D and emPHasis-10. Perceived impact of Covid-19 and related regulations and measures were assessed using a set of specific questions and statements. More than two thirds of patients had an unsuspicious HADS-A and HADS-D. Median scores did not differ from baseline for both HADS-A and HADS-D ( = 0.202; = 0.621). Overall, no significant changes in HADS-A or HADS-D categories from baseline to follow up were observed ( = 0.07; = 0.13). QoL did not change between baseline and follow-up. The Covid-19 pandemic had little impact on access to medical care and established PAH therapy. Patients were in agreement with governmental measures and regulations and felt sufficiently safe. First waves of Covid-19 pandemic had little impact on anxiety, depression and QoL in patient with PAH. Established PAH therapy and access to medical care were not affected. Further studies on the impact of prolonged duration of the ongoing Covid-19 pandemic are needed.
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http://dx.doi.org/10.3389/fpsyt.2021.668647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263927PMC
June 2021

Prevalence of Mental Disorders and Impact on Quality of Life in Patients With Pulmonary Arterial Hypertension.

Front Psychiatry 2021 31;12:667602. Epub 2021 May 31.

Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.

Mental health may affect the quality of life (QoL) in patients with pulmonary arterial hypertension (PAH). However, mental disorders have not been systematically assessed in these patients. We examined the prevalence of mental disorders using structured interviews and determined their impact on QoL in patients with PAH. This study included 217 patients with PAH from two German referral centers. Psychiatric disorders were assessed using the structured clinical interview for DSM-V. QoL was assessed using the WHO Quality of Life questionnaire (short form). The diagnostic value of the Hospital Anxiety and Depression Scale was evaluated by receiver operating characteristic curve analysis. More than one third of the patients had psychological disorders with current or past adjustment disorder (38.2%), current major depressive disorder (23.0%), and panic disorder (15.2%) being the most prevalent mental illnesses. About half of the patients with a history of adjustment disorder developed at least one other mental illness. The presence of mental disorders had a profound impact on QoL. The Hospital Anxiety and Depression Scale ruled out panic disorder and depression disorder with negative predictive values of almost 90%. Mental disorders, in particular adjustment disorder, major depression, and panic disorder, are common in patients with PAH and contribute to impaired QoL in these patients. The Hospital Anxiety and Depression Scale may be used as a screening tool for the most common mental health disorders. Future studies need to address interventional strategies targeting mental disorders in patients with PAH.
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http://dx.doi.org/10.3389/fpsyt.2021.667602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200462PMC
May 2021

Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart.

Clin Res Cardiol 2021 Jun 10. Epub 2021 Jun 10.

Department of Cardiology, Kerckhoff-Klinik GmbH, Benekestr 2-8, 61231, Bad Nauheim, Germany.

Objective: 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.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1007/s00392-021-01884-1DOI Listing
June 2021

Validity of echocardiographic tricuspid regurgitation gradient to screen for new definition of pulmonary hypertension.

EClinicalMedicine 2021 Apr 5;34:100822. Epub 2021 Apr 5.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Centre (UGMLC, Member of the German Centre for Lung Research (DZL), Klinikstrasse 32, 35392, Germany.

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.
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http://dx.doi.org/10.1016/j.eclinm.2021.100822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102717PMC
April 2021

Supplementation with Iron in Pulmonary Arterial Hypertension. Two Randomized Crossover Trials.

Ann Am Thorac Soc 2021 06;18(6):981-988

National Heart and Lung Institute and.

Iron deficiency, in the absence of anemia, is common in patients with idiopathic and heritable pulmonary arterial hypertension (PAH) and is associated with a worse clinical outcome. Oral iron absorption may be impeded by elevated circulating hepcidin concentrations. The safety and benefit of parenteral iron replacement in this patient population is unclear. To evaluate the safety and efficacy of parenteral iron replacement in PAH. In two randomized, double-blind, placebo-controlled 12-week crossover studies, 39 patients in Europe received a single infusion of ferric carboxymaltose (Ferinject) (1,000 mg or 15 mg/kg if weight <66.7 kg) or saline as placebo, and 17 patients in China received iron dextran (Cosmofer) (20 mg iron/kg body weight) or saline placebo. All patients had idiopathic or heritable PAH and iron deficiency at entry as defined by a serum ferritin <37 μg/L or iron <10.3 μmol/L or transferrin saturations <16.4%. Both iron treatments were well tolerated and improved iron status. Analyzed separately and combined, there was no effect on any measure of exercise capacity (using cardiopulmonary exercise testing or 6-minute walk test) or cardiopulmonary hemodynamics, as assessed by right heart catheterization, cardiac magnetic resonance, or plasma NT-proBNP (N-terminal-pro hormone brain natriuretic peptide) at 12 weeks. Iron repletion by administration of a slow-release iron preparation as a single infusion to patients with PAH with iron deficiency without overt anemia was well tolerated but provided no significant clinical benefit at 12 weeks. Clinical trial registered with ClinicalTrials.gov (NCT01447628).
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http://dx.doi.org/10.1513/AnnalsATS.202009-1131OCDOI Listing
June 2021

A novel non-invasive and echocardiography-derived method for quantification of right ventricular pressure-volume loops.

Eur Heart J Cardiovasc Imaging 2021 Feb 28. Epub 2021 Feb 28.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Klinikstrasse 32, Giessen 35392, Germany.

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 < 0.001}, with low bias [-0.016 mmHg/mL (Ees), 0.1225 (Ees/Ea), and -39.0 mmHg mL (stroke work)] and acceptable limits of agreement. Echocardiographic and PW-derived Ees were also tightly correlated, with low bias (-0.009 mmHg/mL) and small limits of agreement. Echocardiographic and conductance-derived Ees, Ees/Ea, and stroke work were also tightly correlated in the validation cohort (rho = 0.9014, 0.9812, and 0.9491, respectively; all P < 0.001), with low bias (0.0173 mmHg/mL, 0.0153, and 255.1 mmHg mL, respectively) and acceptable limits.

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.
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http://dx.doi.org/10.1093/ehjci/jeab038DOI Listing
February 2021

Right ventricular pressure-volume loop shape and systolic pressure change in pulmonary hypertension.

Am J Physiol Lung Cell Mol Physiol 2021 05 3;320(5):L715-L725. Epub 2021 Mar 3.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), German Center for Lung Research (DZL), Giessen, Germany.

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, < 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, < 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.
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http://dx.doi.org/10.1152/ajplung.00583.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174826PMC
May 2021

CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension.

Eur Respir J 2021 04 1;57(4). Epub 2021 Apr 1.

University of Giessen, Dept of Cardiology and Angiology, Giessen, Germany.

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein (CILP)1 in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another nine mice underwent sham surgery. CILP1 protein expression was analysed in all hearts using Western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001) and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in receiver operating characteristic analysis (area under the curve (AUC) 0.79). There was no significant difference between the AUCs of CILP1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) (AUC 0.82). High CILP1 (cut-off value for maladaptive RV of ≥4373 pg·mL) was associated with lower tricuspid annular plane excursion/pulmonary artery systolic pressure ratios (p<0.001) and higher NT-proBNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH.
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http://dx.doi.org/10.1183/13993003.01192-2019DOI Listing
April 2021

Pulmonary complications of tyrosine kinase inhibitors in myeloproliferative disorders.

Eur Respir J 2020 10 29;56(4). Epub 2020 Oct 29.

University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL) and of the Excellence Cluster Cardio-Pulmonary Institute (CPI), Giessen, Germany.

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http://dx.doi.org/10.1183/13993003.02653-2020DOI Listing
October 2020

Advanced risk stratification of intermediate risk group in pulmonary arterial hypertension.

Pulm Circ 2020 Oct-Dec;10(4):2045894020961739. Epub 2020 Oct 7.

Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany.

In 301 treatment-naïve 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.
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http://dx.doi.org/10.1177/2045894020961739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545769PMC
October 2020

Impact of SARS-CoV-2 pandemic on pulmonary hypertension out-patient clinics in Germany: a multi-centre study.

Pulm Circ 2020 Jul-Sep;10(3):2045894020941682. Epub 2020 Jul 23.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

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.
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http://dx.doi.org/10.1177/2045894020941682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378724PMC
July 2020

Risk assessment in severe pulmonary hypertension due to interstitial lung disease.

J Heart Lung Transplant 2020 10 25;39(10):1118-1125. Epub 2020 Jun 25.

Department of Internal Medicine, Justus-Liebig University Giessen, Giessen, Germany. Electronic address:

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 <2.0 liter/min/m) due to ILD who were enrolled in the Giessen PH Registry after being referred for invasive diagnostic work-up of suspected PH during 1995‒2018. A truncated ESC/ERS risk stratification scheme (based on 8 parameters from the full scheme) was applied. Kaplan-Meier and univariate Cox regression analyses were used to evaluate transplant-free survival and hazard ratios, respectively.

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.
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http://dx.doi.org/10.1016/j.healun.2020.06.014DOI Listing
October 2020

Right ventricular dyssynchrony: from load-independent right ventricular function to wall stress in severe pulmonary arterial hypertension.

Pulm Circ 2020 Apr-Jun;10(2):2045894020925759. Epub 2020 May 18.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

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.
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http://dx.doi.org/10.1177/2045894020925759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235672PMC
May 2020

Flow rate variance of a fully implantable pump for the delivery of intravenous treprostinil in pulmonary arterial hypertension.

Pulm Circ 2020 Jan-Mar;10(1):2045894020910136. Epub 2020 Mar 13.

German Center for Lung Research (DZL), Giessen, Germany.

Implantable infusion pumps might improve the convenience and safety of intravenous treprostinil for pulmonary arterial hypertension. The LENUS Pro® 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.
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http://dx.doi.org/10.1177/2045894020910136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074510PMC
March 2020

When it all comes down to pressure: right ventricular ejection fraction at cardiac catheterisation.

Eur Respir J 2020 03 12;55(3). Epub 2020 Mar 12.

University of Giessen and Marburg Lung Center (UGMLC), member of the German Center for Lung Research (DZL) and of the Excellence Cluster Cardio-Pulmonary Institute (CPI), Giessen, Germany.

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http://dx.doi.org/10.1183/13993003.02341-2019DOI Listing
March 2020

Alterations in Doppler-derived renal venous stasis index during recompensation of right heart failure and fluid overload in a patient with pulmonary hypertension.

Rev Cardiovasc Med 2019 Dec;20(4):263-266

Department of Internal Medicine II, Division of Pulmonology and Critical Care Medicine, University Hospital Giessen and Marburg, 35392, Giessen, Germany.

Renal congestion is becoming recognized as a potential contributor to cardiorenal syndromes. Adequate control of congestion with simultaneous preservation of renal function has been proposed as a central goal of the management of heart failure. We report our care of a 48-year-old woman suffering from right heart failure and massive fluid overload due to severe pulmonary hypertension secondary to a combination of left-heart disease and status after recurrent pulmonary embolisms. Alterations in Doppler-derived intrarenal venous flow patterns and a novel renal venous stasis index were used to evaluate improvement in renal venous congestion during recompensation. Due to refractory congestion despite optimal medical treatment and continuous veno-venous hemodialysis, a peritoneal dialysis catheter was placed to relieve the massive ascites. The paracentesis of ascites led to a significant loss of weight, normalization of hydration status with subsequent termination of continuous veno-venous hemodialysis, and a significant improvement in clinical and echocardiographic parameters. Renal Doppler ultrasonography showed continuous improvement in intrarenal venous flow patterns and the renal venous stasis index indicative of effective decongestion up to a normal intrarenal venous flow pattern and renal venous stasis index. Furthermore, residual renal function increased during follow-up. This case demonstrates the feasibility of renal Doppler ultrasonography as a simple, non-invasive, and integrative measure of renal congestion. The renal venous stasis index and intrarenal venous flow patterns may be useful to evaluate the treatment response and to guide therapy in patients with right heart failure.
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http://dx.doi.org/10.31083/j.rcm.2019.04.564DOI Listing
December 2019

Association of right atrial conduit phase with right ventricular lusitropic function in pulmonary hypertension.

Int J Cardiovasc Imaging 2020 Apr 8;36(4):633-642. Epub 2020 Jan 8.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

Alterations of right atrial (RA) function have emerged as determinants of outcome in pulmonary hypertension (PH). We aimed to clarify the pathophysiological associations of impaired RA conduit function with right ventricular (RV) function in PH. In 51 patients with PH (48 with pulmonary arterial hypertension), RA conduit function was assessed as echocardiographic peak early diastolic strain rate (PEDSR). PEDSR and cardiac magnetic resonance parameters were measured within 24 h of right heart catheterization and generation of pressure-volume loops to assess RV diastolic (RV end-diastolic pressure [EDP] and relaxation [Tau]) and systolic function. Spearman rho correlation and linear regression analysis were used to determine the association of PEDSR with RV function. The impact of PEDSR on time to clinical worsening was assessed using Kaplan-Meier and Cox regression analyses. Median (interquartile range) PEDSR was - 0.56 s -  (- 1.08 to - 0.37). Impaired PEDSR was significantly correlated with RV diastolic stiffness [EDP (rho = 0.570; p < 0.001) and Tau (rho = 0.500; p < 0.001)] but not with RV contractility or coupling. In multivariate linear regression including parameters of RV lusitropic and inotropic function, EDP remained independently associated with impaired PEDSR. During a median follow-up of 9 months, 23 patients deteriorated. After multivariate adjustment, PEDSR remained associated with clinical worsening (hazard ratio: 2.85; 95% confidence interval: 1.20-6.78). Altered RV lusitropy is associated with impaired RA conduit phase. PEDSR emerged as a promising, non-invasive, bedside-ready parameter to evaluate RV diastolic function and to predict prognosis in PH.
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http://dx.doi.org/10.1007/s10554-019-01763-xDOI Listing
April 2020

Pending Right Heart Failure in Healthy Preterm-Born Subjects?

Am J Respir Crit Care Med 2020 04;201(8):1008-1009

Free University of BrusselsBrussels, Belgium.

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http://dx.doi.org/10.1164/rccm.201911-2188LEDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159413PMC
April 2020

Right ventricular function correlates of right atrial strain in pulmonary hypertension: a combined cardiac magnetic resonance and conductance catheter study.

Am J Physiol Heart Circ Physiol 2020 01 22;318(1):H156-H164. Epub 2019 Nov 22.

Department of Internal Medicine, Justus Liebig University Giessen, Universities of Giessen and Marburg Lung Center, German Center for Lung Research, Giessen, Germany.

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 () and RV-arterial coupling [ratio of end-systolic elastance to arterial elastance (/)]. 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. / was 0.73 [0.48-1.08], and was 0.14 mmHg/mL [0.05-0.22]. RV diastolic impairment [RV end-diastolic pressure (EDP) and ] was correlated with RA phasic function, but and 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, 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. 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.
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http://dx.doi.org/10.1152/ajpheart.00485.2019DOI Listing
January 2020

Against the Odds: Risk Stratification with Cardiac Magnetic Resonance Imaging in Pulmonary Arterial Hypertension.

Am J Respir Crit Care Med 2020 02;201(4):403-405

Justus Liebig University GiessenUniversities of Giessen and Marburg Lung CenterGiessen, Germany.

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http://dx.doi.org/10.1164/rccm.201910-2069EDDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049925PMC
February 2020

Doppler-Derived Renal Venous Stasis Index in the Prognosis of Right Heart Failure.

J Am Heart Assoc 2019 11 19;8(21):e013584. Epub 2019 Oct 19.

Division of Pulmonology and Critical Care Medicine Department of Internal Medicine II University Hospital Giessen and Marburg Giessen Germany.

Background Persistent congestion with deteriorating renal function is an important cause of adverse outcomes in heart failure. We aimed to characterize new approaches to evaluate renal congestion using Doppler ultrasonography. Methods and Results We enrolled 205 patients with suspected or prediagnosed pulmonary hypertension (PH) undergoing right heart catheterization. Patients underwent renal Doppler ultrasonography and assessment of invasive cardiopulmonary hemodynamics, echocardiography, renal function, intra-abdominal pressure, and neurohormones and hydration status. Four spectral Doppler intrarenal venous flow patterns and a novel renal venous stasis index (RVSI) were defined. We evaluated PH-related morbidity using the Cox proportional hazards model for the composite end point of PH progression (hospitalization for worsening PH, lung transplantation, or PH-specific therapy escalation) and all-cause mortality for 1-year after discharge. The prognostic utility of RVSI and intrarenal venous flow patterns was compared using receiver operating characteristic curves. RVSI increased in a graded fashion across increasing severity of intrarenal venous flow patterns (<0.0001) and was significantly associated with right heart and renal function, intra-abdominal pressure, and neurohormonal and hydration status. During follow-up, the morbidity/mortality end point occurred in 91 patients and was independently predicted by RVSI (RVSI in the third tertile versus referent: hazard ratio: 4.72 [95% CI, 2.10-10.59; <0.0001]). Receiver operating characteristic curves suggested superiority of RVSI to individual intrarenal venous flow patterns in predicting outcome (areas under the curve: 0.789 and 0.761, respectively; =0.038). Conclusions We propose RVSI as a conceptually new and integrative Doppler index of renal congestion. RVSI provides additional prognostic information to stratify PH for the propensity to develop right heart failure. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT03039959.
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http://dx.doi.org/10.1161/JAHA.119.013584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898799PMC
November 2019

Acute response to rapid iloprost inhalation using the Breelib™ nebulizer in pulmonary arterial hypertension: the Breelib™ acute study.

Pulm Circ 2019 Jul-Sep;9(3):2045894019875342. Epub 2019 Sep 11.

Department of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

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.
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http://dx.doi.org/10.1177/2045894019875342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6740066PMC
September 2019

Impaired right ventricular lusitropy is associated with ventilatory inefficiency in pulmonary arterial hypertension.

Eur Respir J 2019 11 21;54(5). Epub 2019 Nov 21.

Dept of Internal Medicine, Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany.

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 ( / ) slope >48, was evaluated using logistic regression analysis.The median (interquartile range) of the / slope was 42 (32-52) and the / nadir was 40 (31-44). The mean±sd of peak end-tidal carbon dioxide tension ( ) was 23±8 mmHg. Ea, Eed and parameters reflecting pulmonary arterial stiffness (capacitance and distensibility) correlated with the / slope, / nadir, 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 (p<0.10).Our data suggest that impaired RV lusitropy and increased afterload are associated with ventilatory inefficiency in PAH.
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http://dx.doi.org/10.1183/13993003.00342-2019DOI Listing
November 2019

Validation of the Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio for the Assessment of Right Ventricular-Arterial Coupling in Severe Pulmonary Hypertension.

Circ Cardiovasc Imaging 2019 09 10;12(9):e009047. Epub 2019 Sep 10.

Department of Internal Medicine (K.T., A.D., H.A.G., E.M., W.S., N.S., H.G., M.J.R.), Justus-Liebig-University Giessen, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Germany.

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 <0.805). Patients with TAPSE/PASP <0.31 mm/mm Hg had a significantly worse prognosis than those with higher TAPSE/PASP.

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.
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http://dx.doi.org/10.1161/CIRCIMAGING.119.009047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099862PMC
September 2019
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