Right Ventricular Function in Pulmonary Hypertension

PD Dr. Khodr Tello

Right ventricular (RV) function is the main determinant of symptomatology and outcome in pulmonary arterial hypertension (PAH). However, guidelines for the diagnosis and treatment of pulmonary hypertension (PH) do not advise on how best to measure RV function in these patients. Conventional RV functional parameters, derived from echocardiography or cardiac magnetic resonance imaging (cMRI), are dependent on pre- and afterload and do not necessarily mirror inherent RV function. To define and assess load-independent RV contractility, a combination of in-depth heart physiological and clinical assessment is needed. Over the past years, evidence has shown that the RV functional adaptation in severe PH is homeometric, with increased contractility matching the increased afterload, as similarly known for the left ventricle. The gold-standard measure of RV contractility is end-systolic elastance (Ees) derived from pressure-volume loops and defined by the end-systolic pressure (ESP) versus end-systolic volume (ESV) relationship. To assess the adequacy of RV contractile adaptation to afterload, Ees is expressed in relation to pulmonary arterial elastance (Ea), defined by an ESP versus stroke volume (SV) relationship. The Ees/Ea ratio is a measure of the interplay between the right ventricle and the pulmonary artery, also known as RV-pulmonary arterial (PA) coupling. Ees can be measured from a family of pressure-volume loops at decreasing venous return (the multi-beat method) or by a single-beat method relying on the determination of a maximum pressure (Pmax) from nonlinear extrapolation of early and late isovolumic portions of the RV pressure curve (before maximal and after minimal dP/dt, respectively)

Research gaps in this important area that have been addressed by Khodr Tello`s group are:

• the validation of non-invasive and invasive surrogate measures of RV-PA coupling (Tello K et al. Am J Respir Crit Care Med 2018; 198: 816-818, Tello K et al. Circ Cardiovasc Imaging 2019; 12: e009047, Richter MJ…Tello K Am J Respir Crit Care Med 2020; 201: 116-119)
• the introduction and establishment of non-invasive RV pressure-volume loops to measure Ees/Ea in daily clinical routine (Tello K et al. Int J Cardiol 2018; 266: 229-235. Tello K et al JACC Cardiovasc Imaging 2019; 12: 2155-2164, Richter MJ, …Tello K. Eur Heart J Cardiovasc Imaging 2022; 23: 498-507);
• the definition of the RV point of uncoupling, at which Ea exceeds Ees and increasing afterload is not matched by an increase in contractility (Tello K et al. Circ Heart Fail 2019; 12: e005512, Kremer N…Tello K. Unmasking right ventricular-arterial uncoupling during fluid challenge in pulmonary hypertension. J Heart Lung Transplant 2022; 41: 345-355);
• the prognostic and clinical relevance of RV-PA coupling based on clinical data (Richter MJ,… Tello K. Am J Respir Crit Care Med 2020; 201: 116-119) ;
• RV contractility and diastolic function in comparison to exercise capability (Tello K et al. Eur Respir J 2019; 54: 1900342);
• possible differences between the sexes in RV-PA coupling in PH (Tello K et al. Am J Respir Crit Care Med 2020; 202: 1042-1046);
• the impact of approved drugs for PH on RV contractility (Tello K et al. Am J Respir Crit Care Med 2022; and
• the role of RV function in risk stratification of PAH (Tello K et al. Eur Respir J 2019; 54: 1802435, Ghio S, …Tello K, investigators TiP. A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension. Eur Respir J 2020; 56: 2000513.).

In addition to the presented contribution to the field of RV function, further ongoing and planned projects will cover the following current research gaps in interventricular and heart-lung interaction:

1. diastolic RV dysfunction and its impact on prognosis in PH;
2. the impact of targeted medication on RV inherent load-independent function;
3. interventricular dependence in heart failure with preserved EF (HFpEF) and HFpEF-PH;
4. RV function in lung cancer;
5. loss of RV reserve in an in-depth 3D model of the right ventricle;
6. COVID-19-associated RV-PA coupling impairment and possible reasons for post-COVID-associated dyspnea; and
7. impact of sepsis, acute respiratory distress syndrome (ARDS), and ARDS-related therapeutic regimens (such as positive end-expiratory pressure [PEEP] and prone positioning) on RV function;

Key projects are summarized in Figure 1 and described in more detail below

Figure 1. Overview of key planned and ongoing research projects. ARDS, acute respiratory distress syndrome; cMRI, cardiac magnetic resonance imaging; echo, echocardiography; HFpEF, heart failure with preserved ejection fraction; ICU, intensive care unit; PA, pulmonary arterial; PAWP, pulmonary arterial wedge pressure; PEEP, positive end-expiratory pressure; PH, pulmonary hypertension; RHC, right heart catheterization; RV, right ventricular.

Contact

PD Dr. Khodr Tello
Station 2.5 Pneumologie/Intensivmedizin

Klinikstr. 33
35392 Giessen

Tel: +49 (0) 641 985 56087 (office)
Tel: +49 (0) 641 98  542687

Email:
Khodr.Tello@innere.med.uni-giessen.de

Ten most important publications:

1. Tello K, Richter MJ, Axmann J, Buhmann M, Seeger W, Naeije R, Ghofrani HA, Gall H. More on Single-Beat Estimation of Right Ventriculoarterial Coupling in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2018; 198: 816-818.
2. Richter MJ, Peters D, Ghofrani HA, Naeije R, Roller F, Sommer N, Gall H, Grimminger F, Seeger W, Tello K. Evaluation and Prognostic Relevance of Right Ventricular-Arterial Coupling in Pulmonary Hypertension. Am J Respir Crit Care Med 2020; 201: 116-119.
3. Tello K, Dalmer A, Vanderpool R, Ghofrani HA, Naeije R, Roller F, Seeger W, Wilhelm J, Gall H, Richter MJ. Cardiac Magnetic Resonance Imaging-Based Right Ventricular Strain Analysis for Assessment of Coupling and Diastolic Function in Pulmonary Hypertension. JACC Cardiovasc Imaging 2019; 12: 2155-2164.
4. Tello K, Dalmer A, Axmann J, Vanderpool R, Ghofrani HA, Naeije R, Roller F, Seeger W, Sommer N, Wilhelm J, Gall H, Richter MJ. Reserve of Right Ventricular-Arterial Coupling in the Setting of Chronic Overload. Circ Heart Fail 2019; 12: e005512.
5. Tello K, Ghofrani HA, Heinze C, Krueger K, Naeije R, Raubach C, Seeger W, Sommer N, Gall H, Richter MJ. A simple echocardiographic estimate of right ventricular-arterial coupling to assess severity and outcome in pulmonary hypertension on chronic lung disease. Eur Respir J 2019; 54: 1802435.
6. Tello K, Dalmer A, Vanderpool R, Ghofrani HA, Naeije R, Roller F, Seeger W, Dumitrescu D, Sommer N, Brunst A, Gall H, Richter MJ. Impaired right ventricular lusitropy is associated with ventilatory inefficiency in pulmonary arterial hypertension. Eur Respir J 2019; 54: 1900342.
7. Tello K, Richter MJ, Yogeswaran A, Ghofrani HA, Naeije R, Vanderpool R, Gall H, Tedford RJ, Seeger W, Lahm T. Sex Differences in Right Ventricular-Pulmonary Arterial Coupling in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med 2020; 202: 1042-1046.
8. Tello K, Kremer N, Richter MJ, Gall H, Muenks J, Ghofrani A, Schermuly R, Naeije R, Kojonazarov B, Seeger W. Inhaled Iloprost Improves Right Ventricular Load-Independent Contractility in Pulmonary Hypertension. Am J Respir Crit Care Med 2022.
9. Ghio S, Mercurio V, Fortuni F, Forfia PR, Gall H, Ghofrani A, Mathai SC, Mazurek JA, Mukherjee M, Richter M, Scelsi L, Hassoun PM, Tello K, investigators TiP. A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension. Eur Respir J 2020; 56: 2000513.
10. Kremer N, Rako Z, Douschan P, Gall H, Ghofrani HA, Grimminger F, Guth S, Naeije R, Rieth A, Schulz R, Seeger W, Tedford RJ, Vadasz I, Vanderpool R, Wiedenroth CB, Richter MJ, Tello K. Unmasking right ventricular-arterial uncoupling during fluid challenge in pulmonary hypertension. J Heart Lung Transplant 2022; 41: 345-355.

Here you can find all ILH-publications

Funding

Group members:

Research Fellows

Dr Zvonimir Rako, Nils Kremer, Selin Yildiz, Ashkan Tolou, Athithan Yogeswaran

Doctoral students

Yascha Seyed Vossoughi, Herbst Sophie, Bruno Brita da Rocha: End-diastolic stiffness under exercise, Johannes Wiedemann: Liver elastography in patients with pulmonary hypertension, Merle Wiegand, Anne Brunst, Dana Peters, Antonia Dalmer, Heinze Charlotte