A. Vonk Noordegraaf

Fasudil reduces monocrotaline-induced pulmonary arterial hypertension: comparison with bosentan and sildenafil

Pulmonary arterial hypertension (PAH) still cannot be cured, warranting the search for novel treatments. Fasudil (a Rho kinase inhibitor) was compared with bosentan (an endothelin receptor blocker) and sildenafil (a phosphodiesterase 5 inhibitor), with emphasis on right ventricular (RV) function, in a reversal rat model of monocrotaline (MCT)-induced PAH. In addition, the effects of combining bosentan or sildenafil with fasudil were studied. MCT (40 mg·kg body weight−1) induced clear PAH in male Wistar rats (n = 9). After 28 days, echocardiography, RV catheterisation and histochemistry showed that cardiac frequency, stroke volume and RV contractility had deteriorated, accompanied by RV dilatation and hypertrophy, and marked pulmonary arterial wall thickening. Mean pulmonary arterial pressure and pulmonary vascular resistance increased significantly compared to healthy rats (n = 9). After 14 days, MCT-treated rats received a 14-day oral treatment with bosentan, sildenafil, fasudil or a combination of fasudil with either bosentan or sildenafil (all n = 9). All treatments preserved cardiac frequency, stroke volume and RV contractility, and reduced pulmonary vascular resistance and RV dilatation. Fasudil lowered RV systolic pressure and mean pulmonary arterial pressure significantly, by reducing pulmonary arterial remodelling, which reduced RV hypertrophy. Combining bosentan or sildenafil with fasudil had no synergistic effect. Fasudil significantly improved PAH, to a greater degree than did bosentan and sildenafil.

Multidisciplinary convalescence recommendations after gynaecological surgery: a modified Delphi method among experts

Please cite this paper as: Vonk Noordegraaf A, Huirne J, Brölmann H, van Mechelen W, Anema J. Multidisciplinary convalescence recommendations after gynaecological surgery: a modified Delphi method among experts. BJOG 2011;118:1557–1567.

eHealth Program to Empower Patients in Returning to Normal Activities and Work After Gynecological Surgery: Intervention Mapping as a Useful Method for Development

Background Full recovery after gynecological surgery takes much longer than expected regardless of surgical technique or the level of invasiveness. After discharge, detailed convalescence recommendations are not provided to patients typically, and postoperative care is fragmented, poorly coordinated, and given only on demand. For patients, this contributes to irrational beliefs and avoidance of resumption of activities and can result in a prolonged sick leave. Objective To develop an eHealth intervention that empowers gynecological patients during the perioperative period to obtain timely return to work (RTW) and prevent work disability. Methods The intervention mapping (IM) protocol was used to develop the eHealth intervention. A literature search about behavioral and environmental conditions of prolonged sick leave and delayed RTW in patients was performed. Patients’ needs, attitudes, and beliefs regarding postoperative recovery and resumption of work were identified through focus group discussions. Additionally, a literature search was performed to obtain determinants, methods, and strategies for the development of a suitable interactive eHealth intervention to empower patients to return to normal activities after gynecological surgery, including work. Finally, the eHealth intervention was evaluated by focus group participants, medical doctors, and eHealth specialists through questionnaires. Results Twenty-one patients participated in the focus group discussions. Sufficient, uniform, and tailored information regarding surgical procedures, complications, and resumption of activities and work were considered most essential. Knowing who to contact in case of mental or physical complaints, and counseling and tools for work reintegration were also considered important. Finally, opportunities to exchange experiences with other patients were a major issue. Considering the determinants of the Attitude–Social influence–self-Efficacy (ASE) model, various strategies based on a combination of theory and evidence were used, resulting in an eHealth intervention with different interactive functionalities including tailored convalescence recommendations and a video to communicate the most common pitfalls during the perioperative period to patients and employers. Fifteen patients in the focus groups, 11 physicians, and 3 eHealth specialists suggested points for improvement to optimize the usability of the eHealth intervention and judged it an approachable, appropriate, and attractive eHealth intervention to empower gynecological patients. Conclusions The IM protocol was a useful method to develop an eHealth intervention based on both theory and evidence. All patients and stakeholders judged the eHealth intervention to be a promising tool to empower gynecological patients during the perioperative period and to help them to return to normal activities and work.

Improvement of cardiac imaging in electrical impedance tomography by means of a new electrode configuration

Until now, electrical impedance tomography (EIT) has been used for cardiac imaging with the electrodes attached transversally at the level of the fourth intercostal space at the anterior side. However, the results obtained with this electrode configuration have been disappointing. The aim of the present study was to improve the measurement design of EIT for cardiac imaging. Therefore, magnetic resonance imaging (MRI) scans were analysed in two healthy subjects to determine the optimum anatomical plane in which atria and ventricles are clearly visually separated. From these findings, we proposed a new oblique plane at the level of the ictus cordis anteriorly and 10 cm higher posteriorly. EIT pictures obtained in the oblique plane revealed a better visual separation between the ventricles and atria than with the electrodes attached in the transverse plane. Comparison between volume changes measured by means of MRI and impedance changes in different regions of interest measured with EIT were performed with the electrodes in the proposed oblique plane. Ventricular and atrial volume changes measured by MRI show the same pattern as do impedance changes measured by EIT. Furthermore, we assessed the reproducibility and validity of the oblique electrode configuration in ten healthy mate volunteers during rest and during exercise compared with the currently used transverse electrode configuration. The reproducibility coefficient assessed from repeated measurements with the electrodes attached in the oblique plane was 0.98 at rest and 0.85 during exercise. For the transverse plane the reproducibility coefficient was 0.96 at rest and 0.66 during exercise. The well-known increase in stroke volume during exercise is 40% in healthy subjects. The increase in impedance change during exercise compared with rest was 34 +/- 13% (20-59%) for the oblique plane and 68 +/- 57% (13-140%) for the transverse plane. From these results we infer that the stroke volume is assessed more accurately by using the oblique plane. From these findings, we conclude that the oblique plane improved the cardiac measurements, because (i) a better spatial separation of the heart compartments is obtained, (ii) the results are more reliable and (iii) measurements during exercise are more accurate with the electrodes attached in an oblique plane.

Right ventricular function in scleroderma-related pulmonary hypertension

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.

Pressure-overload-induced right heart failure

Although pulmonary arterial hypertension originates in the lung and is caused by progressive remodeling of the small pulmonary arterioles, patients die from the consequences of pressure-overload-induced right heart failure. Prognosis is poor, and currently there are no selective treatments targeting the failing right ventricle. Therefore, it is of utmost importance to obtain more insights into the mechanisms of right ventricular adaptation and the transition toward right heart failure. In this review, we propose that the same adaptive mechanisms, which initially preserve right ventricular systolic function and maintain cardiac output, eventually initiate the transition toward right heart failure.

The striated muscles in pulmonary arterial hypertension: adaptations beyond the right ventricle

Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive remodelling of the small pulmonary vessels. The daily-life activities of patients with PAH are severely limited by exertional fatigue and dyspnoea. Typically, these symptoms have been explained by right heart failure. However, an increasing number of studies reveal that the impact of the PAH reaches further than the pulmonary circulation. Striated muscles other than the right ventricle are affected in PAH, such as the left ventricle, the diaphragm and peripheral skeletal muscles. Alterations in these striated muscles are associated with exercise intolerance and reduced quality of life. In this Back to Basics article on striated muscle function in PAH, we provide insight into the pathophysiological mechanisms causing muscle dysfunction in PAH and discuss potential new therapeutic strategies to restore muscle dysfunction. RV, LV, diaphragm and peripheral muscle dysfunction contributes to reduced quality of life in PAH patients http://ow.ly/NAyZP

Non-invasive evaluation of left ventricular function by means of impedance cardiography

Background: Simple, accurate, continuous non‐invasive cardiac monitoring during the peri‐ and postoperative periods for patients at risk of cardiac failure would be very useful. Electrical impedance cardiography (EIC) has been proposed as an accurate method for non‐invasive measurement of cardiac function. However, in recent years the accuracy of EIC in stroke volume (SV) measurement has been questioned and this prevented global acceptance of the method. Beside SV, EIC is capable of measuring several other left ventricular contractility indices, which are measured directly from the impedance signal. The aim of this study was to compare these variables with the echocardiographically derived left ventricular wall motion score (WMS) as the reference method.

Right ventricular ejection fraction and NT-proBNP are both indicators of wall stress in pulmonary hypertension

Although many therapeutic options have become available in recent years for the treatment of pulmonary arterial hypertension (PAH), there is still no cure available. The primary cause of death is right ventricular failure. Therefore, monitoring right ventricular function is a way to guide therapeutic decisions and a logical step forward to improve life expectancy in PAH patients. Although magnetic resonance imaging (MRI) is considered the gold standard in measuring right ventricular function, the technique is expensive with limited accessibility; therefore, it is unlikely to be frequently used in PAH centres on a regular basis. Therefore, technically simpler methods are welcomed. In current issue of the European Respiratory Journal , Blyth et al. 1 report that N-terminal B-type natriuretic peptide (NT-proBNP) might act as a simple and effective alternative to MRI measurement. Thus, the results of Blyth et al. 1 confirm those of earlier studies suggesting a relationship between cardiac function in PAH …

Corrigendum to: 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism

[Eur Heart J 2014; 35 :3033–73, doi:10.1093/eurheartj/ehu283] The published version of these Guidelines referred to 317 000 VTE-related deaths related in …