Nicolaas Westerhof

Nicolaas Westerhof
Amsterdam University Medical Center | VUmc · Department of Pulmonary Medicine

Ph.D.

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520
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Publications

Publications (520)
Article
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The generally accepted view of the arterial system as a single uniform tube with a distal reflection site is an oversimplification. It cannot reproduce important actual findings. The findings could be reproduced by a more detailed model. The uniform tube should be abandoned as conceptual model. HIGHLIGHTS •The arterial system is often likened to u...
Article
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Introduction: Pressure waveshape derived parameters such as the augmentation index are related to unfavourable cardiovascular events [1]. Wave reflections determine wave shape [2], however, several findings seem to contradict the current views. Current view. The arterial system can be modelled by a tube with a reflection site at the end: the heart...
Article
Objective: In hypertension research aortic pressure wave travel and wave shape play a central role. Presently the explanation of aortic pressure is mainly based on wave travel and reflection in tube models with a single distal reflection. Increased pulse pressure with age is assumed to result from increased magnitude of distal reflection (higher S...
Article
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The function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension. While much progress has been made in the treatment of pulmonary hypertension, therapies for the RV are less well established. In this review of treatment strategies for the RV, first we focus on ways to reduce wall stress since this is the mai...
Chapter
This chapter starts by a brief review of coronary physiology in terms of pressure-flow relationships and effects of vessel distensibility on microvascular resistance to lay the foundation for interpretation of coronary stenosis hemodynamics. The fluid dynamics of stenosis pressure gradient, resistance, and its dependency on flow and stenosis dimens...
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Lung resection is a standard treatment in patients with clinical stages I and II and selected patients with stage IIIA nonsmall cell lung cancer [1]. Major lung resection (MLR), such as (bi)lobectomy or pneumonectomy, occasionally lead to pulmonary hypertension (PH). Several studies report an increase in pulmonary artery pressures in about one-thir...
Article
In pulmonary arterial hypertension (PAH), upfront combination therapy is associated with better clinical outcomes and a greater reduction in N-terminal pro-brain natriuretic peptide (NT-proBNP) than monotherapy. NT-proBNP levels reflect right ventricular (RV) wall stress, which increases when the right ventricle dilates. This study explored the imp...
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This paper aims to summarize and map contemporary views on some contentious aspects of arterial hemodynamics that have remained unresolved despite years of research. These were discussed during a workshop entitled Arterial hemodynamics: past, present and future held in London on June 14 and 15, 2016. To do this we formulated a list of potential con...
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In idiopathic pulmonary arterial hypertension (PAH), increased pulmonary vascular resistance is associated with structural narrowing of small (resistance) vessels and increased vascular tone. Current information on pulmonary vascular remodeling is mostly limited to averaged increases in wall thickness, but information on number of vessels affected...
Article
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Pressure and flow are travelling waves and are reflected at many locations. The forward and reflected waves, obtained by wave separation, are compound waves. This compounded character of the reflected wave explains why its magnitude decreases with increased peripheral resistance, why it appears to run forward rather than backward, and why its retur...
Article
In pulmonary hypertension, the right ventricle adapts to the increasing vascular load by enhancing contractility (“coupling”) to maintain flow. Ventriculoarterial coupling implies that stroke volume changes little while preserving ventricular efficiency. Ultimately, a phase develops where ventricular dilation occurs in an attempt to limit the reduc...
Article
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Pulmonary hypertension (PH) resulting from left heart failure is an increasingly recognized clinical entity. To distinguish isolated postcapillary PH from combined post‐ and precapillary PH, the use of a diastolic pressure gradient (DPG = diastolic Pulmonary Artery Pressure − Pulmonary Arterial Wedge Pressure, dPAP − PAWP) has been advocated over t...
Article
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During aging, systolic blood pressure continuously increases over time, whereas diastolic pressure first increases and then slightly decreases after middle age. These pressure changes are usually explained by changes of the arterial system alone (increase in arterial stiffness and vascular resistance). However, we hypothesise that the heart contrib...
Article
Introduction: The SU5416+Hypoxia (SuHx) rat model a commonly used model of severe pulmonary arterial hypertension (PAH). Previous studies have shown that to induce PH in rats, administration of SU5416 alone is insufficient, but when administered together with a second hit such as hypoxia or immune modification, severe angioproliferative PH will en...
Article
Introduction: Idiopathic Pulmonary Arterial Hypertension (iPAH) is a fatal lung disease characterized by remodeling of the lung vasculature leading to a 5-fold increase of the pulmonary vascular resistance (PVR). Quantitative information on vascular remodeling is limited to assessments of increased wall thickness, and the extent of internal diamete...
Article
The aim of this study was to evaluate the effects of renal denervation on pulmonary vascular remodeling and cardiac function in two pulmonary artery hypertension (PAH) animal models. Methods: PAH was induced in male rats by a single injection of monocrotaline (60mg/kg; s.c.; MCT model; n=9/group) or by sugen 5416 (25mg/kg; s.c.) followed by 4 weeks...
Article
We thank Davies et al1 for their important and opposing remarks. Let us begin with a sincere apology. You rightfully indicate that instantaneous wave-free ratio (iFR) was incorrectly defined in the text. We realized this error just after the proofs were approved and have corrected the errors in the meantime. Please see the correction note in Hyper...
Article
Unlabelled: In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient...
Article
Wave separation analysis and wave intensity analysis (WIA) use (aortic) pressure and flow to separate them in their forward and backward (reflected) waves. While wave separation analysis uses measured pressure and flow, WIA uses their derivatives. Because differentiation emphasizes rapid changes, WIA suppresses slow (diastolic) fluctuations of the...
Article
Right ventricular (RV) diastolic stiffness is increased in pulmonary arterial hypertension (PAH) patients. We investigated whether RV diastolic stiffness is associated with clinical progression and assessed the contribution of RV wall thickness to RV systolic and diastolic stiffness. Using single-beat pressure-volume analyses, we determined RV end-...
Article
Rationale: Exercise tolerance is decreased in patients with pulmonary hypertension (PH). It is unknown whether exercise intolerance in PH coincides with an impaired rest-to-exercise response in right ventricular (RV) contractility. Objectives: To investigate in patients with PH the RV exertional contractile reserve, defined as the rest-to-exerci...
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The most common feature of pulmonary hypertension (PH) on computed tomography pulmonary angiography (CTPA) is an increased diameter-ratio of the pulmonary artery to the ascending aorta (PA/AAAX). The aim of this study was to investigate whether combining PA/AAAX measurements with ventricular measurements improves the predictive value of CTPA for pr...
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not needed. Copyright © 2014, American Journal of Physiology - Heart and Circulatory Physiology.
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Background: Even after years of stable response to therapy, patients with idiopathic pulmonary arterial hypertension (IPAH) may show an unexpected clinical deterioration due to progressive right ventricular (RV) failure. Therefore, the aim of this study was to assess in 5-year clinically stable patients with IPAH whether initial differences or sub...
Article
See related article, pp 85–92 The article by Zamani et al1 shows a clear association between the major systemic arterial parameters vascular resistance (SVR) and total arterial compliance (TAC, inverse of arterial stiffness) and left ventricular (LV) mass and LV wall/LV cavity volume ratio (here called remodeling, for short). The forward and backw...
Article
Background: After lung transplantation, increased left ventricular (LV) filling can lead to LV failure, increasing the risk of post-operative complications and mortality. LV dysfunction in pulmonary arterial hypertension (PAH) is characterized by a reduced LV ejection fraction and impaired diastolic function. Objectives: The pathophysiology of L...
Article
The SU5416 combined with hypoxia (SuHx) rat model features angio-obliterative pulmonary hypertension resembling human pulmonary arterial hypertension. Despite increasing use of this model, a comprehensive haemodynamic characterisation in conscious rats has not been reported.We used telemetry to characterise haemodynamic responses in SuHx rats and a...
Article
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Right ventricular (RV) diastolic function is impaired in patients with pulmonary arterial hypertension (PAH). Our previous study showed that elevated cardiomyocyte stiffness and myofilament Ca2+ sensitivity underlie diastolic dysfunction in PAH. This study investigates protein modifications contributing to cellular diastolic dysfunction in PAH. RV...
Article
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To assess the contribution of right ventricular (RV) trabeculae and papillary muscles (TPM) to RV mass and volumes in controls and patients with pulmonary arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP) during follow-up. 50 patients u...
Article
The role that the right ventricle (RV) plays in the body circulation is only recently acknowledged. Especially in disease states, RV function may be of great importance. As such, knowledge on RV function in both health and disease is essential for clinicians. The present chapter provides current knowledge available on RV function, starting with a b...
Article
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Respiratory influences are a major confounder when evaluating central hemodynamics during exercise. We studied four different methods to assess mean pulmonary artery pressure (mPAP) and pulmonary capillary wedge pressure (PCWP) in case of respiratory swings.Central hemodynamics were measured simultaneously with esophageal pressure during exercise i...
Article
The role of right ventricular (RV) diastolic stiffness in pulmonary arterial hypertension (PAH) is not well-established. Therefore, we investigated the presence and possible underlying mechanisms of RV diastolic stiffness in PAH-patients. Single-beat RV pressure-volume analyses were performed in 21 PAH-patients and 7 controls to study RV diastolic...
Article
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Introduction: Exercise variables determined in patients with pulmonary arterial hypertension (PAH) at the time of diagnosis, predict survival. It is unknown whether upon treatment, subsequent changes in these exercise variables reflect improvements in survival. The aim of this study was to determine changes in exercise variables in PAH patients an...
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Abstract Glucose metabolism measurement using 2-deoxy-2-[(18)F]-fluoro-d-glucose ((18)FDG) positron emission tomography (PET) could provide in vivo information about pulmonary vascular remodeling. The purpose of this study was to assess whether pulmonary (18)FDG uptake in idiopathic pulmonary arterial hypertension (IPAH) patients changes and, if so...
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Arterial pressure and flow waves travel and are reflected. Waveform analysis and wave separation gave insight into these phenomena and parameters thus obtained are indicators of cardiovascular events. However, the interpretation of forward and reflected waves is still not generally agreed upon. We used an anatomically accurate (data from Hickson, 2...
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A subgroup of patients with idiopathic pulmonary arterial hypertension (IPAH) has severely reduced diffusion capacity for carbon monoxide (DL,CO) and poor prognosis. Their characteristics are currently unknown. The aim of this study is to contrast clinical characteristics and treatment responses of IPAH-patients with a severely reduced and more pre...
Article
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Purpose: Pulmonary arterial hypertension (PAH) and pulmonary hypertension secondary to (diastolic) heart failure requires different clinical management. Current guidelines recommend the use of pulmonary capillary wedge pressure (PCWP) to distinguish both conditions. However, within a patient PCWP is quite variable depending on volume-state. Therefo...
Article
Objectives: In treatment of hypertension not only the pressure response is of interest, but also the effect on arterial parameters, for example, stiffness and resistance, is essential. We therefore reviewed what quantitative information on arterial stiffness can be obtained from pressure wave analysis. Methods: Using data from published large co...
Article
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In pulmonary hypertension and other conditions, such as acute respiratory distress syndrome and left heart failure, right ventricular dysfunction is a prognostic determinant. Therefore, functional parameters pertaining to the right heart alone, i.e. independent of its loading conditions, should be used to quantify right ventricular disease progress...
Article
BACKGROUND: End-systolic elastance (E(es)), a load-independent measure of ventricular function, is of clinical interest for studies of the right ventricle (RV) in patients with pulmonary arterial hypertension (PAH). The objective of this study was to determine whether, in PAH patients, E(es) can be estimated from mean pulmonary artery pressure (mPA...
Article
BACKGROUND: In pulmonary arterial hypertension (PAH), high right ventricular (RV) power output requires increased myocardial oxygen consumption. Oxygen supply, however, does not increase in proportion. It is unknown what cellular mechanisms underlie this lack of adaptation. We therefore determined oxygen supply parameters in RV tissue slices of dec...
Article
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We previously demonstrated that diaphragm muscle weakness is present in experimental pulmonary arterial hypertension (PH). However, the nature of this diaphragm weakness is still unknown. Therefore the aim of this study was to investigate whether changes at the sarcomeric level contribute to diaphragm weakness in PH. For this purpose, in control ra...
Article
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Arterial compliance is mainly determined by the elasticity of proximal large-conduit arteries of which the aorta is the largest contributor. Compliance forms an important part of the cardiac load and plays a role in organ (especially coronary) perfusion. To follow local changes in aortic compliance, as in aging, noninvasive determination of complia...
Article
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Background: Pulmonary hypertension (PH) is a well-recognized complication of COPD. The impact of PH on exercise tolerance is largely unknown. We evaluated and compared the circulatory and ventilatory profiles during exercise in patients with COPD without PH, with moderate PH, and with severe PH. Methods: Forty-seven patients, GOLD (Global Initia...
Article
Increased large artery stiffness is a major determinant of systolic pressure and indicator of cardiovascular events. The reflected wave, its arrival time (return time) and magnitude, contributes to systolic pressure, and is a supposed indicator of aortic stiffness. With aortic stiffening, the return time is assumed to decrease inversely with PWV as...
Article
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Arterial input impedance, as complete description of the arterial system, is explained by waves and wave reflection. Without wave reflections input impedance would equal aortic characteristic impedance and pressure and flow wave shapes would be similar. Waves reflect at many locations, causing input impedance to deviate from aortic characteristic i...
Article
Decrease in arterial compliance leads to an increased pulse pressure, as explained by the Windkessel effect. Pressure waveform is the sum of a forward running and a backward running or reflected pressure wave. When the arterial system stiffens, as a result of aging or disease, both the forward and reflected waves are altered and contribute to a gre...
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It is generally known that positive pressure ventilation is associated with impaired venous return and decreased right ventricular output, in particular in patients with a low right atrial pressure and relative hypovolaemia. Altered lung mechanics have been suggested to impair right ventricular output in COPD, but this relation has never been firml...