Search

Background According to current guidelines, the diagnosis of pulmonary hypertension (PH) relies on echocardiographic probability followed by right heart catheterization. How echocardiography predicts PH recently re-defined by a mean pulmonary artery pressure (mPAP) >20 mmHg instead of ≥25 mmHg and pulmonary vascular disease defined by a pulmonary vascular resistance (PVR) >3 or >2 Wood units has not been established. Methods A total of 278 patients referred for PH underwent a comprehensive echocardiography followed by a right heart catheterization. Fifteen patients (5.4%) were excluded because of insufficient quality echocardiography. Results With PH defined by a mPAP >20 mmHg, 23 patients had no PH, 146 had pre-capillary and 94 post-capillary PH. At univariate analysis, maximum velocity of tricuspid regurgitation (TRV) ≥2.9 and ≤3.4 m/s, left ventricle (LV) eccentricity index >1.1, right ventricle (RV) outflow tract (OT) notching or acceleration time 1 and PA diameter predicted PH, whereas inferior vena cava diameter and right atrial area did not. At multivariable analysis, only TRV ≥2.9 m/s independently predicted PH. Additional independent prediction of PVR >3 Wood units was offered by LV eccentricity index >1.1 and RVOT acceleration time 20 mmHg, mPAP ≥25 mmHg, mPAP >20 mmHg + PVR >2 Wood units and mPAP ≥25 mmHg + PVR >3 Wood units are illustrated in Figure 1A–D. Conclusions Echocardiography as recommended in current guidelines can be used to assess the probability of re-defined PH in a referral center. However, the added value of indirect signs is modest and sufficient quality echocardiographic signals may not be recovered in some patients. Funding Acknowledgement Type of funding sources: None.

Background Transthoracic echocardiogram is the most important non-invasive screening tool for pulmonary hypertension (PH), but right heart catheterization (RHC) remains mandatory to establish the diagnosis. According to the current guidelines, the echocardiographic probability of PH is based on the combination of direct and indirect signs. In the 6th World Symposium on Pulmonary Hypertension, PH has been defined as mean pulmonary artery pressure (mPAP) >20 mmHg, and pulmonary vascular resistance (PVR) ≥3 WU. Aim To validate the echocardiographic direct and indirect signs of PH suggested by the guidelines in view of the new definition of PH in patients who underwent echocardiography and RHC. Methods All consecutive patients referred between January 2018 and December 2019 to undergo RHC for suspected PH were prospectively enrolled in the study. Echocardiography was performed within one hour from indicated RHC. Results Overall, 263 patients were enrolled: 33 (13%) had normal pulmonary pressures, and 230 (87%) had PH. Among the 230 patients with PH, 136 (59%) had pre-capillary and 94 (41%) had post-capillary PH. All underwent echocardiography within one hour from RHC. At univariable logistic regression test, tricuspid regurgitant jet (TRJ) >2.9 m/sec [OR 8.32 (3.15–26.37, p1.1 [OR 5.57 (2.44–14.41, p25 mm [OR 4.74 (2.01–13.09, p=0.001)], right-to-left ventricle basal diameter >1 [OR 4.54 (1.83–13.74, p=0.003)], and early diastolic pulmonary regurgitation velocity >2.2 m/sec [OR 3.14 (1.07–13.46, p=0.067)], predicted PH, whereas dilated inferior vena cava and right atrial area did not. At multivariable analysis, only TRJ >2.9 m/sec [OR 7.95 (2.78–27.07, p1.1 [OR 4.89 (1.75–15.35, p=0.004)] showed a positive correlation to PH. The best area under the curve (AUC, 0.86) for predicting PH was obtained with TVR >2.9 m/sec + 2 indirect signs (sensitivity 0.77, specificity 0.94). Non-invasive estimate of mPAP showed a good correlation to invasive measurement (regression coefficient β 16.8±0.7, p Conclusions Echocardiographic direct and indirect signs of PH as suggested by the current guidelines should be used to assess the probability of PH being present. Echocardiographic measurements have high accuracy (low bias) and moderate precision (acceptable limits of agreement) The best area under the curve for predicting PH according to the new definition (mPAP >20 mmHg and PVR ≥3 WU) can be obtained with TVR >2.9 m/sec + 2 indirect signs. Funding Acknowledgement Type of funding sources: None. Figure 1

Background Careful, step-wise assessment is required in all patients with an atrial septal defect (ASD) to exclude pre-existing pulmonary vascular disease or left ventricular disease. Fluid challenge test (FCT) and balloon occlusion testing (BOT) may unmask left ventricular disease and challenge the pulmonary circulation, but their complementary role in the evaluation of patients with “operable” ASD is not well established. Aim To evaluate the haemodynamic changes of the pulmonary circulation by FCT and BOT in ASD patients undergoing percutaneous closure according to the current guidelines. Methods Consecutive patients selected for percutaneous ASD closure underwent invasive hemodynamic assessment at baseline and after BOT, FCT and both. Results Fifty patients (mean age 47.3±11.7 years, 72% female) were included. All patients had a pulmonary-to-systemic flow ratio (QP/QS) ≥1.5, pulmonary vascular resistance (PVR) FCT caused a marked increase in pulmonary blood flow of almost 2 liters (p0.1). No difference was observed in the PAWP response to FCT, BOT or both between groups; no patients reached a PAWP ≥18 mmHg following FCT or BOT alone, but 4 (8%) patients did following the addition of FCT to BOT. No acute clinical adverse events were experienced by any patients. Conclusions None of the reported ASD patients presented with FCT criteria of post-capillary PH (that is a PAWP >18 mmHg). Even small rises in PVR may have significant implications on cardiovascular haemodynamics. In fact, patients with PVR Funding Acknowledgement Type of funding sources: None. Figure 1

Altitude is associated with a decrease in partial pressure of oxygen. Hypoxia induces pulmonary vasoconstriction with subsequent fixed increase in pulmonary artery pressure, and eventual right heart failure.High altitude exposure is associated with an increase in pulmonary artery pressure that is proportional to initial vasoconstriction. Echocardiographic evaluations on a large number of subjects show that the altitude-induced increase in pulmonary pressure is generally modest and does not exceed the 25mmHg that are diagnostic of pulmonary hypertension. This does not greatly increase right ventricular afterload, so that imaging of the right ventricle only shows some alterations of indices of systolic or diastolic function, but preserved contractile reserve during exercise. In less than 1% of cases, hypoxic vasoconstriction is strong and may be a cause of severe pulmonary hypertension and right heart failure.The prognostic relevance of altitude-induced pulmonary hypertension and associated cardiac function alterations is not known. Treatment of hypoxic pulmonary hypertension relies on evacuation to a lower altitude, oxygen and pulmonary vasodilators. These treatment strategies have not been rigorously evaluated.Altitude may be a cause of right heart failure. This uncommon complication of altitude exposure requires further epidemiological and therapeutic studies.

Exercise testing provides additional information over resting variables and is a standard of care in the assessment of coronary artery disease with less subsequent cardiovascular events. In pulmonary hypertension (PH), right ventricular function is clearly an important determinant of survival. However, right ventricular impairment is currently assessed only during resting conditions. Exercise (stress) testing may provide further insight into the complex paradigm of right ventricular dysfunction, right ventricular–left ventricular interdependence and right ventricular–pulmonary artery coupling. Whether pulmonary artery pressure ( P pa)–flow relationships during exercise provides a window into earlier diagnosis of functionally significant PH or adds incrementally to our armamentarium of diagnostic tests and prognostic indicators in PH, is a topic of ongoing investigation. In this issue of the European Respiratory Journal ( ERJ ), the studies by Kovacs et al. [1] and Whyte et al. [2] discuss the potential clinical utility of identifying “normal” and “abnormal” pulmonary vascular response patterns to exercise in patients aged ≤50 yrs. The clinical significance of a hypertensive P pa response to exercise is currently uncertain. It may reflect a normal variant without clinical significance, or it may reflect a bona fide cardiopulmonary limitation and abnormal phenotype. In support of the latter, asymptomatic relatives of individuals with established idiopathic or familial PH have demonstrated an abnormal response to exercise [3]. Few studies have used right heart catheterisation (RHC) to address whether mean P pa ( P pa) >30 mmHg during exercise represents an aberrant pulmonary vascular system in “at-risk” populations [4–11]. Recently, Tolle et al. [9] evaluated a large cohort with exertional dyspnoea who underwent simultaneous cardiopulmonary exercise testing (CPET) and RHC. At maximal exercise, P pa and pulmonary vascular resistance (PVR) were highest, while resting pulmonary arterial hypertension was lowest in …

A moderate pulmonary hypertension is a hallmark of experimental, as well as clinical, acute lung injury. Pulmonary hypertension in acute lung injury, appears to be caused primarily by a partially reversible increase in extra-alveolar vascular closing pressure, the latter being modulated by vasodilating products of the cyclooxygenase pathway of arachidonic acid metabolism, as well as by an endogenous release of nitric oxide. Gas exchange in acute lung injury is improved by increased pulmonary vascular tone. However it is also improved by inhaled nitric oxide, which increases perfusion to the better aerated lung areas. Whether pharmacological interventions aimed at the prevention of right ventricular failure in acute lung injury improve right ventriculo-vascular coupling sufficiently to exert a favourable influence on outcome, remains to be shown.

General anesthetics interfere with arterial and ventricular mechanical properties, often altering left ventricular-arterial (LVA) coupling. We hypothesized that sevoflurane and propofol alter LVA coupling by different effects on arterial and ventricular properties.Experiments were conducted in six anesthetized open-chest dogs for the measurement of left ventricular pressure and aortic pressure and flow. Measurements were performed during anesthesia with 0.5, 1.0 and 1.5 minimum alveolar concentration sevoflurane and 12, 24 and 36 mg/kg/h propofol. LVA coupling was assessed as the ratio of ventricular end-systolic elastance (E(es), measuring ventricular contractility) to effective arterial elastance (E(a), measuring ventricular afterload). The steady component of afterload, arterial tone, was assessed by systemic vascular resistance and arterial pressure-flow curves. The pulsatile component of afterload was assessed by aortic impedance and compliance.Sevoflurane decreased aortic pressure and cardiac output more than propofol. Sevoflurane reduced arterial tone, increased arterial stiffness and did not affect wave reflections. It increased E(a), decreased E(es) and reduced LVA coupling. Propofol reduced arterial tone, did not affect arterial stiffness and decreased wave reflections. It did not affect E(a), E(es) or LVA coupling.Sevoflurane increased ventricular afterload and decreased ventricular performance, thereby altering LVA coupling. Propofol did not affect ventricular afterload or ventricular performance, thereby preserving LVA coupling. Thus, propofol preserves LVA coupling in dogs better, and might be a better choice for patients with compromised left ventricular function.

Pulmonary arterial hypertension (PAH) is a rare syndrome of fatigue and dyspnoea, caused by increased pulmonary vascular resistance and right heart failure without an identifiable pulmonary or cardiac cause. Despite important recent advances in treatment the condition remains incurable.Experimental animal models of PAH rely on hypoxic or monocrotaline injected rodents, the creation of left to right shunts in lambs or piglets, ligation of the ductus arteriosus in newborn lambs, genetically manipulated rodents and tissue culture. Hypoxic pulmonary hypertension is usually only moderate and limited to medial hypertrophy with varying degrees of adventitial change, but may progress to extensive remodelling in some species. Monocrotaline induced pulmonary hypertension is severe with prominent medial hypertrophy, inflammatory adventitial remodelling and, initially, pulmonary oedema and endothelial apoptosis. Pulmonary hypertension induced by shunting remains the most realistic model of PAH but causes only moderate increase in vascular resistance due to medial hypertrophy. Pulmonary hypertension of the newborn is severe but largely vasospastic, with predominant medial hypertrophy. An increasing number of genetically manipulated rodents are becoming available for the investigation of specific signalling pathways.While none of the models has yet reproduced PAH each allows investigation of a specific hypothesis. Recent progress has resulted from genetic manipulation and molecular and cellular approaches.Animal models of PAH share basic biological abnormalities which, together with the study of lung tissue from patients with severe disease should lead to better understanding of the pathology and therapeutic innovation.

Cardiovascular responses to volume loading are often described with reference to Frank-Starling’s law of the heart. However, the exact formulation of this law, and how it effectively applies to various haemodynamic conditions is not always clear. It may therefore be useful to revisit the original observations by Otto Frank and Ernest Starling, anddiscuss the different ventricular function curves that have been derived from their pioneer experiments.

Pulmonary arterial hypertension (PAH) is a syndrome of dyspnea, fatigue, chest pain and syncope defined by an increase in pulmonary vascular resistance (PVR) of unknown cause. The pathobiology of PAH remains incompletely understood. The gene of the idiopathic form of PAH (IPAH) has been located on chromosome 2, and shown to present mutations of a sequence that encodes for a transforming growth factor receptor, bone morphogenenetic protein receptor 2 (BMPR2). Severe pulmonary hypertension is associated with an increased expression of the angiogenic factor, angiopoietin-1, which shuts off the expression of BMPR1A, a transmembrane protein necessary for BMPR2 signalling, and thereby causes pulmonary artery smooth muscle cell proliferation. Additional biological abnormalities have been identified at all pulmonary arterial wall compartments of PAH patients. The endothelium produces an excess of endo-thelin, a potent vasoconstrictor and mitogenic mediator, while synthesis and release of antagonistic prostacyclin and nitric oxide is decreased. Pulmonary vascular smooth muscle cells present with an increased expression of a serotonin transporter, allowing for vasoconstrictive and mitogenic effects of increased circulating serotonin, and also show an increased expression of voltage-dependent potassium channels, which also promotes vasoreactivity and proliferation. The adventitial matrix bound metalloprotases appear to be activated in relation to increased serine elastase, leading to increased production of tenascin, a potent mitogen. While none of these abnormalities isolately explains PAH, their identification has already led to efficient therapeutic interventions, including the administration of prostacyclin derivatives and anti-endothelin compounds.

To review the perioperative anaesthetic management of pulmonary arterial hypertension.Extraction from Pubmed database of French and English articles on the perioperative anaesthetic management of pulmonary hypertension for 9 years.The collected articles were reviewed and selected according their quality and originality. The more recent data were selected.Pulmonary arterial hypertension is classically divided in primary and secondary. Primary pulmonary hypertension (familial and sporadic) is relatively severe and rare. Muscularization of the terminal portion of the pulmonary vascular arterial tree, caused by smooth muscle cell hyperplasia is the first change. Pulmonary arterial hypertension linked with disorders of the respiratory system and hypoxemia or pulmonary venous hypertension including mitral valve disease and chronic left ventricular dysfunction are often associated with high morbidity and mortality. The main consequence of pulmonary hypertension development is the occurrence of right-sided circulatory failure. A better understanding of disease pathophysiology will contribute to the development of new therapies increasing then the prognosis of these patients. The management of primary pulmonary hypertension or secondary pulmonary arterial hypertension is a challenge for the anaesthesiologist because the risk of right ventricular failure is markedly increased.

Measurement of continuous blood flow by thermodilution catheter takes into account measures that are intermittent, though the estimation of mean pressures is satisfactory. Natural pulsatile pulmonary circulation would remain unknown. To evaluate pulsatile pulmonary hemodynamics and its importance in right ventricular function, the calculation of impedance based on spectral analysis of pressure and flow waves would allow their respective contributions to resistance, elastance and wave reflection upon after right ventricle loading. Computerization allows bedside monitoring of this sophisticated assessment of right ventricle after loading.

The 1-, 3-, and 5-year survival rates of the patients included in the National Institute of Health Registry on Primary Pulmonary Hypertension were 77%, 41%, and 27% respectively. It is unclear to what extent better applied conventional therapy contributes to improved survival rates that now are reported with calcium-channel blockers, prostacyclin, or even transplantation. To date, by far the most favorable results are reported with high-dose calcium-channel blockers combined with anticoagulant therapy, with survival rates at 3 years approximately 100%. It has to be emphasized, however, that such exceptionally favorable results are to be expected only in a small minority of patients who should not be considered to be cured because, sooner or later, their disease will continue to evolve. Further improvements obviously are needed for most patients with PAH. Interesting developments are likely in the coming years, with new multidrug approaches to control pulmonary vasoreactivity and remodeling and, hopefully, also with progress in lung transplantation. The past 2 decades have witnessed important progress in the treatment of PAH. Although significant improvements in quality of life and survival rate have been obtained with prostacyclin therapy, and better perspectives now are offered with atrial septostomy and lung transplantation, conventional therapy also has evolved. Patients now are counseled more adequately regarding how to remain physically active while avoiding exercise-induced anginal pain or syncope. Invasive and potentially risky medical procedures have been restricted in favor of noninvasive and functional evaluations whenever possible. Risk factors such as appetite suppressants, pregnancy, and hypobaric hypoxia are now better appreciated. The indications of supplemental oxygen, inotropic agents, and diuretics have been refined based on improved pathophysiologic understanding. Most patients now benefit from anticoagulant therapy with coumarin derivatives, although some uncertainty remains about the optimal international normalized ratio to be achieved. Safer acute reversibility testing now is performed with fewer and shorter-acting agents that are more specific to the pulmonary circulation to select the small proportion of patients who benefit from long-term high-dose calcium-channel blocker therapy.

Pulmonary embolism alters the distribution of ventilation/perfusion relationships, and increases pulmonary vascular resistance. These changes lead to hypoxemia and hypocapnia, and eventually, to right heart failure. The thin-walled and compliant right ventricle adapts to any increase in afterload by dilatation and decreased stroke volume, but this is largely prevented or delayed by the pulmonary circulation being a low resistance, recruitable and distensible circuit. Pulmonary embolism cannot be associated with a mean pulmonary artery pressure higher than 40 mmHg. More severe pulmonary hypertension indicates the presence of a hypertrophied right ventricle in the context of preexistent cardiac or pulmonary disease. Gas exchange is initially affected because of increased ventilation/perfusion ratios in embolized lung areas, and decreased ventilation/perfusion ratios in remaining non embolized lung areas. Both physiologic shunt and physiologic dead space increase accordingly, resulting in hypoxemia and hypocapnia. However, these changes are rapidly affected by an increase in ventilation, and by a "pneumoconstriction" which decreases physiologic dead space in embolized areas. In addition, a series of secondary alterations contribute to increase perfusion to lung units with low ventilation/perfusion ratios, thereby aggravating hypoxemia, while hypocapnia persists.

Doping is defined as the administration of or use by competing athletes of any substance foreign to the body or of any physiological substance taken in abnormal quantity or taken by an abnormal route of entry into the body with the sole intention of increasing in an artificial and unfair manner his/her performance in competition. The prevalence of doping has been estimated by rigorous methods to be 5-15%. The only two dopings of established efficacy are: anabolic steroids for resistive performance, and blood doping for endurance performance. Although medical control of athletes is reputably poor, reported accidents attributable to doping have been until now very rare. Doping is unfair, and must as such be banned from competitions. Medicalized doping is unethical. More studies are required to improve knowledge of doping as a public health issue. Sports medicine is in need of scientific and moral revalorization.

Acute respiratory failure is an acute insufficiency of the gas exchange function of the lungs. Respiratory failure is always associated with abnormal arterial blood gases, in the sense that the gradient between alveolar PO2 (PAO2) and arterial PO2 (PaO2) (AaPO2) is increased, while PaCO2 is increased, normal or decreased. Respiratory failure therefore is classically defined using arterial blood gases criteria, generally by a PaO2 lower than 60 mmHg and a PaCO2 higher than 50 mmHg. Accordingly, pulmonary gas exchange in patients admitted to the intensive care unit are evaluated with repetitive arterial blood gas analysis. However, PaO2 and PaCO2 are determined not only by the gas exchange function of the lungs, but also by extrapulmonary factors including inspired PO2 (PIO2) and mixed venous PO2 (PvO2) which in turn depends on cardiac output (Q), O2 extraction, haemoglobin, and P50. Also, the tolerance to abnormal PaO2 and PaCO2 is largely dependent on the patient’s past history and current illness.

Pulmonary vascular pressure measurements throughout the world are made with the Swan-Ganz catheter, which was introduced in 1970 [1], This catheter is balloon-tipped, which allows placement in the pulmonary artery without fluoroscopic control and measurement successively of right atrial pressure (Pra), right ventricular pressure (Prv), pulmonary artery pressure (Ppa) and occluded Ppa (Ppao). It has two fluid-filled lumens, one for measurement of Ppa and Ppao, and one for the measurement of Pra and injection of saline into the right atrium for the measurement of pulmonary blood flow (Q) by thermodilution. It has a thermistor at the tip for measurement of blood temperature in the pulmonary artery.

This study sought to determine the site of increased pulmonary vascular resistance (PVR) in primary pulmonary hypertension by standard bedside hemodynamic evaluation.The measurement of pulmonary vascular pressures at several levels of flow (Q) allows the discrimination between active and passive, flow-dependent changes in mean pulmonary artery pressure (Ppa), and may detect the presence of an increased pulmonary vascular closing pressure. The determination of a capillary pressure (Pc') from the analysis of a Ppa decay curve after balloon occlusion allows the partitioning of PVR in an arterial and a (capillary + venous) segment. These approaches have not been reported in primary pulmonary hypertension.Ppa and Pc' were measured at baseline and after an increase in Q induced either by exercise or by an infusion of dobutamine, at a dosage up to 8 microg/kg body weight per min, in 11 patients with primary pulmonary hypertension. Reversibility of pulmonary hypertension was assessed by the inhalation of 20 ppm nitric oxide (NO), and, in 6 patients, by an infusion of prostacyclin.At baseline, Ppa was 52+/-3 mm Hg (mean value+/-SE), Q 2.2+/-0.2 liters/min per m2, and Pc' 29+/-3 mm Hg. Dobutamine did not affect Pc' and allowed the calculation of an averaged extrapolated pressure intercept of Ppa/Q plots of 34 mm Hg. Inhaled NO had no effect. Prostacyclin decreased Pc' and PVR. Exercise increased Pc' to 40+/-3 mm Hg but did not affect PVR.ns. These findings are compatible with a major increase of resistance and reactivity at the periphery of the pulmonary arterial tree.

Pulmonary hypertension secondary to chronic pulmonary venous hypertension in patients with congestive heart failure may become relatively fixed over time due to structural changes in the pulmonary vasculature [1]. An acute decrease in left atrial pressure (Pia) after cardiac transplantation in these patients may therefore be associated with high pulmonary arterial pressures (Ppa), persistent at levels known to be poorly tolerated by a normal right ventricle [2]. Accordingly, high preoperative pulmonary vascular resistance (PVR) has been found associated with a significant risk of fatal right ventricular (RV) failure after orthotopic cardiac transplantation [3–6]. In order to limit the frequency of this complication, patients with a PVR of more than 480 to 640 dynes.s.cm5 (6 to 8 Wood units) are generally excluded from the potential benefits of the surgical procedure [3–6]. Most recently, testing for a pharmacological reversal of elevated PVR at preoperative evaluation has been reported [6,7], and the results of these manipulations contended to be helpful for the prediction of postoperative pulmonary hemodynamics [6].

of only mean pulmonary artery pressure (Ppa) and mean pulmonary blood flow (Q). Accordingly, the functional state of the pulmonary circulation still is currently evaluated by pulmonary vascular resistance (PVR) calculated as a mean pressure/mean flow ratio. However, a simple inspection of pressure and flow tracings recorded in a main pulmonary artery (Fig. 1) reveals that the description of these complex pressure and flow waves by just one number may be an excessive simplification. But how do we know exactly what is lost by ignorance of the natural pulsatility of the pulmonary circulation? This question can be answered by an analysis of the pressure and flow waves in the frequency-domain instead of in the time-domain.