This article appears in the following Rheumatology issue: Update in systemic sclerosis [View the issue table of contents]
Right ventricular function in scleroderma-related pulmonary hypertension
1Department of Pulmonary Diseases, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands and 2Department of Pathophysiology, Faculty of Medicine, Free University of Brussels, Brussels, Belgium.
Correspondence to: A. Vonk Noordegraaf, Department of Pulmonary Diseases, VU University Medical Center, De Boelelaan 1117, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail: A.Vonk{at}VUmc.nl
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Abstract |
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 Top Abstract IntroductionThe heart in SSc:...Haemodynamic and...Future research directionsAcknowledgementsReferences |
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SSc-associated pulmonary arterial hypertension (PAH) has a poorer prognosis than that of other types of pulmonary hypertension. Recent echocardiographic and haemodynamic studies suggest that right ventriculer (RV) pump function and filling characteristics are altered in SSc-PAH as compared with idiopathic PAH. This could be explained by intrinsic myocardial involvement of the disease, related to abnormal collagen deposition, also observed in the left ventricle, or an increased vulnerability to ischaemia due to coronary vasculopathy, abnormal collagen cross-linking and altered myocyte function. It is also possible that a relatively more important decrease in pulmonary arterial compliance as evidenced by recently reported increased characteristic impedance measurements, would contribute to RV-arterial decoupling. More pathological, imaging and haemodynamic studies are needed for a better understanding for relatively more important vulnerability of the RV in SSc-PAH.
KEY WORDS: Right ventricle, Scleroderma, Pulmonary hypertension, Pulmonary artery pressure
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Introduction |
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TopAbstractIntroductionThe heart in SSc:...Haemodynamic and...Future research directionsAcknowledgementsReferences |
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Pulmonary arterial hypertension (PAH) is a common complication in SSc patients, with an estimated prevalence between 7% and 12% [1]. The presence of pulmonary hypertension will lead to the development of right ventricular (RV) hypertrophy as a normal adaptation to increased afterload, but this is eventually followed by RV failure and death. The prognosis of pulmonary hypertension is thus highly dependent on the adaptative capacity of the RV. SSc-PAH has a worse prognosis than idiopathic PAH (IPAH) despite similar baseline haemodynamic characteristics [2, 3]. Although this difference in prognosis might be in part explained by factors such as multiple comorbidities, age-related factors due to the later disease onset of PAH in SSc and the poorer response to therapy, there is increasing evidence that the RV itself could be a primary factor.
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The heart in SSc: pathological studies |
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TopAbstractIntroductionThe heart in SSc:...Haemodynamic and...Future research directionsAcknowledgementsReferences |
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The heart is one of the major organs involved in scleroderma, the involvement of which can be manifested by myocardial disease, conduction system abnormalities, arrhythmias or pericardial disease [4]. Although no pathological studies have been devoted to the RV in SSc-PAH, it seems reasonable to extrapolate results obtained from studies on the left ventricle [LV). It is already known that myocardial fibrosis as well as intramyocardial coronary vessel involvement affect the ventricles in SSc [5]. Fernandes et al. [5] analysed endomyocardial biopsies from SSc patients, with both limited and the diffuse cutaneous forms of SSc, without signs or symptoms of heart failure, PAH, LV hypertrophy and LV diastolic dysfunction [6]. They demonstrated abnormal collagen deposition in 94% of the cases. Impaired contractility of hearts of patients with SSc-PAH might therefore be explained by increased extracellular matrix. Not only the amount of collagen, but also collagen cross-linking might impair ventricular contractility. Cross-linking of collagen has been reported in the skin of SSc patients [7]. It may be speculated that SSc myocardial tissue expresses an increased degree of collagen cross-linking that further contributes to an impaired cardiac contractility.
Another cause of impaired contractility in SSc-PAH could be ischaemia due to coronary artery disease. It has been shown that structural abnormalities of small coronary arteries or arterioles are present in SSc and cause a reduced coronary reserve [7]. In the case of pulmonary hypertension, oxygen demand of the RV is increased, whereas right coronary artery flow is impaired. Thus, with coronary artery disease and high oxygen demand, ischaemia of the RV could directly impair its function. However, this has not been investigated to date.
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Haemodynamic and echocardiographic evidence |
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TopAbstractIntroductionThe heart in SSc:...Haemodynamic and...Future research directionsAcknowledgementsReferences |
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Evidence has accumulated in recent years that RV is more impaired in SSc-PAH than in other types of PAH. Fisher et al. [3] showed that SScPAH patients have a lower mean pulmonary artery pressure in comparison with IPAH [47 mmHg vs 54 mmHg), despite similar levels of cardiac dysfunction as assessed by a cardiac output measurement (cardiac index 2.2 l/min/m2 vs 2.1 l/min/m2) [3]. Although there was echocardiographic evidence for left-sided diastolic dysfunction in the SSc group, the pulmonary artery wedge pressure was normal. RV function was not measured in this study, although no difference was found in RV dimensions between the idiopathic and scleroderma group. RV function can be divided in a contractile part (systolic function) and a filling part (diastolic function). Several echocardiographic studies in SSc-PAH showed RV diastolic dysfunction is common [8–10] even in the presence of normal systolic pulmonary artery pressure, as estimated from maximum velocity of tricuspid regurgitation [10]. To answer the question as to whether this abnormal RV filling pattern could be related to the effects of the disease per se, or to associated pulmonary vasculopathy, Huez et al. [10] performed tissue Doppler examinations at rest and during exercise in SSc patients with normal systolic pulmonary artery pressure and age-matched healthy controls. The results showed a consistent pattern of altered RV diastolic function that was correlated to the acceleration time of pulmonary arterial flow and to the slope of multi-point pulmonary artery pressure–flow plots, suggesting latent pulmonary hypertension as a major cause [10]. Of particular interest was their demonstration of shortened pulmonary flow acceleration time in the presence of an estimated normal pulmonary vascular resistance and therefore essentially explained by a decrease in pulmonary arterial compliance [10]. Recent invasive studies have shown a proportionally more important increase in characteristic impedance in SSc-PAH than in IPAH [4], which could be caused by a proximal pulmonary arterial involvement and disproportionally increased afterload at a given level of pulmonary vascular resistance.
Overbeek et al. [11] recently reported the so called ‘pump function graph’ to describe the relation between mean ventricular pressure and stroke volume in 13 lcSSc-PAH and 17 IPAH patients. The results summarized in Fig. 1 show that for any given mean RV pressure, stroke volume was lower in SSc-PAH than in IPAH, suggesting a decreased contractility. Since stroke volume and exercise capacity are closely related to each other in pulmonary hypertension, this finding provides an explanation for the poor exercise capacity of SSc-PAH patients in comparison with IPAH despite having similar pulmonary artery pressure. In addition, the results also demonstrate that a similar increase in pulmonary artery pressure effects stroke volume more in the SSc-PAH than in iPAH, explaining the early occurrence of RV failure and death in this patient group.
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Qs) than in IPAH (Thus, the presently available literature suggests that both diastolic and systolic function are markedly altered in SSc-PAH. Even though the respective contributions of increased characteristic impedance and decreased contractility to the failure of the RV to increase in proportion to increased afterload is not entirely clear, RV–arterial uncoupling in SSc-PAH is very likely to be of clinical and prognostic relevance.
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Future research directions |
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TopAbstractIntroductionThe heart in SSc:...Haemodynamic and...Future research directionsAcknowledgementsReferences |
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Pulmonary hypertension in SSc is accompanied by an ‘out of proportion’ alteration in RV function. Further studies are needed to explore the nature of RV-decoupling in SSc-PAH and develop adapted therapeutic strategies. It is possible that treatments of established efficacy in PAH may have variable effects on RV–arterial coupling in SSc-PAH.
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Acknowledgements |
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TopAbstractIntroductionThe heart in SSc:...Haemodynamic and...Future research directionsAcknowledgementsReferences |
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Supplement: This paper forms part of the supplement entitled ‘Update in systemic sclerosis’. This supplement was supported by an unrestricted grant from Encysive.
Disclosure statement: The authors have declared no conflicts of interest.
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References |
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[Abstract/Free Full Text]
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