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Review
. 2019 Jan 24;53(1):1801900.
doi: 10.1183/13993003.01900-2018. Print 2019 Jan.

Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update

Anton Vonk Noordegraaf  1 , Kelly Marie Chin  2 , François Haddad  3 , Paul M Hassoun  4 , Anna R Hemnes  5 , Susan Roberta Hopkins  6 , Steven Mark Kawut  7 , David Langleben  8 , Joost Lumens  9   10 , Robert Naeije  11   12
Affiliations
Review

Pathophysiology of the right ventricle and of the pulmonary circulation in pulmonary hypertension: an update

Anton Vonk Noordegraaf et al. Eur Respir J. .

Erratum in

Abstract

The function of the right ventricle determines the fate of patients with pulmonary hypertension. Since right heart failure is the consequence of increased afterload, a full physiological description of the cardiopulmonary unit consisting of both the right ventricle and pulmonary vascular system is required to interpret clinical data correctly. Here, we provide such a description of the unit and its components, including the functional interactions between the right ventricle and its load. This physiological description is used to provide a framework for the interpretation of right heart catheterisation data as well as imaging data of the right ventricle obtained by echocardiography or magnetic resonance imaging. Finally, an update is provided on the latest insights in the pathobiology of right ventricular failure, including key pathways of molecular adaptation of the pressure overloaded right ventricle. Based on these outcomes, future directions for research are proposed.

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Conflict of interest statement

Conflict of interest: A. Vonk Noordegraaf reports grants and speaker fees from Actelion, MSD and GSK, outside the submitted work. Conflict of interest: K.M. Chin reports personal fees for consulting work on clinical trials from Actelion, grants (paid to institution) from Ironwood and Sonivie, personal fees for consulting work for a clinical registry from University of California San Diego, and research grants from the NIH, outside the submitted work. Conflict of interest: F. Haddad has nothing to disclose. Conflict of interest: P.M. Hassoun has nothing to disclose. Conflict of interest: A.R. Hemnes reports personal fees from Actelion, Bayer, Complexa and United Therapeutics, and grants from the CMREF and NIH, outside the submitted work; and in addition has a patent issued: Annamometer (oral mechanism for detection of end-tidal CO2; not referenced in this work). Conflict of interest: S.R. Hopkins is funded by the NIH via research grants to study the pulmonary circulation. Conflict of interest: S.M. Kawut reports non-financial travel support from the ATS and Pulmonary Hypertension Association, grants from Actelion, United Therapeutics, Gilead, Lung Biotech, Bayer and Mallinkrodt, and grants and non-financial support from the CMREF, outside the submitted work and paid to his university; and has served in an advisory capacity (for grant review and other purposes) for United Therapeutics, Akros Pharmaceuticals, GSK and Complexa, Inc., without financial support or in-kind benefits. Conflict of interest: D. Langleben reports grants, personal fees and non-financial support from Actelion and Bayer, personal fees from United Therapeutics and Merck, and grants from Northern Therapeutics, outside the submitted work. Conflict of interest: J. Lumens has nothing to disclose. Conflict of interest: R. Naeije has nothing to disclose.

Figures

FIGURE 1
FIGURE 1
The cardiopulmonary system (CPS): a) function and b) characterisation. MVO2: myocardial oxygen consumption; RV: right ventricle; RA: right atrium; LA: left atrium; LV: left ventricle; Ees: end-systolic elastance; τ: time constant of ventricular relaxation; Eed: end-diastolic elastance; PVR: pulmonary vascular resistance; PAC: pulmonary arterial compliance; Ea: arterial elastance; PAP: pulmonary arterial pressure; PAWP: pulmonary arterial wedge pressure; EF: ejection fraction; CO: cardiac output. Subsystems (or units: heart, respectively its load) are characterised by their intrinsic function, which can be derived from the ventricular pressure–volume relationship and the pulmonary pressure–flow relationship. The system parameters result from cardiopulmonary interaction.
FIGURE 2
FIGURE 2
Right ventricular (RV) pressure–volume analysis. Pressure–volume loops at three different stages: normal (blue), pulmonary hypertension (green) and right ventricular failure (purple). Ees: end-systolic elastance; Ea: arterial elastance; τ: time constant of ventricular relaxation. P=α(eβV−1) describes the diastolic pressure–volume relation. Reproduced and modified from [11] with permission.
FIGURE 3
FIGURE 3
The resistance–compliance relationship: the relationship between pulmonary vascular resistance (PVR) and pulmonary arterial compliance (PAC) is characterised by a constant value of RC-time (i.e. the product of PVR×PAC). PAWP: pulmonary arterial wedge pressure. Reproduced and modified from [11] with permission.
FIGURE 4
FIGURE 4
The mean, systolic and diastolic pulmonary arterial pressure (mPAP, sPAP and dPAP) relationships: relative values of pressures in the pulmonary circulation are tightly related. Reproduced and modified from [57] with permission.
FIGURE 5
FIGURE 5
The mean pulmonary arterial pressure (mPAP)–cardiac output (CO) relationships: the ratio of ΔP/ΔCO in health and disease. PH: pulmonary hypertension; PAH: pulmonary arterial hypertension. Reproduced and modified from [71] with permission.
See this image and copyright information in PMC

References

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