Biomedical subjects

Marion Delcroix

Publications and source records attributed to Marion Delcroix.

11 recordsLinked to original sources

PubMed2006

Advanced therapy may delay the need for transplantation in patients with the Eisenmenger syndrome.

AIMS: Advanced therapies (prostacyclin analogues, endothelin receptor antagonists) are successfully used in the treatment of idiopathic pulmonary arterial hypertension. In addition, patients with the Eisenmenger syndrome (ES) seem to benefit from these news drugs regarding symptoms, but there is still no evidence for changes in outcome. METHODS AND RESULTS: The clinical course of 43 patients (M/F 13/30, age 34.0 +/- 12.7 years), registered with unstable ES in our database, was retrospectively analysed. These patients were divided into two groups: those treated with and those treated without advanced therapy. The primary endpoint was defined as death from any cause. Death or inscription on the active waiting list of heart-lung transplantation was considered as secondary endpoint. Kaplan-Meier survival and log rank testing were performed to determine differences in outcome between the two groups. The total cohort was followed for a median period of 4.9 (range 0.2-14.9) years. Mean survival time for patients treated with (n = 26) and without (n = 17) advanced therapy therapies were 8.5 +/- 1.5 and 8.5 +/- 0.9 years, respectively (log rank testing, P = 0.31). However, the mean time to death or inscription on the active waiting list was significantly longer for patients treated with advanced therapy when compared with those without (7.8 +/- 1.0 vs. 3.4 +/- 0.9 years, P = 0.006). CONCLUSION: For the given follow-up period, no improvement in survival time could be documented in adult patients with unstable ES treated with advanced therapy. However, we might suggest with these data that the need for heart-lung transplantation can be substantially delayed with new drugs.

Adult↗

PubMed2006

Effect of adenovirus-mediated gene transfer of nitric oxide synthase on vascular reactivity of rat isolated pulmonary arteries.

Aerosol gene transfer of endothelial nitric oxide synthase (eNOS) and inducible NOS (iNOS) to rat lungs increased NOS expression and activity, and prevented hypoxic pulmonary vasoconstriction (HPV) in vivo. Hereby, we examined the effect of eNOS and iNOS aerosol gene transfer on the endothelium-dependent relaxation (EDR) and on acute HPV in isolated rat pulmonary arteries. Changes in isometric forces were recorded in organ baths for large conduit arteries (diameter 1.8+/-0.1 mm) and in a wire myograph for small resistance arteries (258+/-35 microm). Male Wistar rats were randomly aerosolized with adenovirus (Ad) encoding beta-galactosidase (control), eNOS, or iNOS. Four days later, exhaled nitric oxide was measured, NOS expression within rat lungs was evaluated by quantitative real-time polymerase chain reaction and immunohistochemistry, vasoconstricting agonist and acetylcholine concentration response curves were generated, and the time course of HPV was recorded. Human eNOS and murine iNOS were expressed within rat lung tissue mostly in parenchyma and endothelial cells. Large arteries isolated from Ad-i, eNOS-aerosolized rats developed lower agonist-induced tension than those of control rats. The first and second contractions of the HPV were smaller in the Ad-i, eNOS-aerosolized rats. Contractions were modestly, but significantly and inversely, related to exhaled NO. Agonist- and hypoxia-induced contractions were even more reduced after eNOS aerosolization. There was no significant effect on EDR and no notable difference between small and large vessels. We conclude that adenovirus (Ad)-mediated NOS gene transfer can counteract both pharmacologically and hypoxia-induced increases in pulmonary vascular tone in isolated rat pulmonary arteries. eNOS seems as efficient as iNOS in regulating pulmonary vascular tone.

Adenoviridae↗

PubMed2005

The evaluation of pulmonary hypertension using right ventricular myocardial isovolumic relaxation time.

Right ventricular (RV) blood pool-derived isovolumic relaxation time (IVRT) correlates well with systolic pulmonary arterial pressure (PAP). However, because of complex parameter derivation, the method is rarely used. The aim of this study was to validate the measurement of myocardial velocity imaging-derived RV IVRT (IVRT') against invasively measured PAP. Transthoracic echocardiography with myocardial velocity imaging and right heart catheterization were performed in 33 patients with pulmonary hypertension. Blood pool IVRT and myocardial IVRTs for the tricuspid valve annulus ring, basal and apical RV free wall segments were measured and compared with data from 33 age- and sex-matched control subjects. Measured IVRTs were significantly longer in patients with pulmonary hypertension than in control subjects. The strongest correlation (R = 0.74, P < .0001) was found between systolic PAP and the heart rate-corrected IVRT' derived from the basal RV free wall segment. The basal segment IVRT' corrected for heart rate correlates well with the invasive PAP measurement and, therefore, can be used to predict systolic PAP. It can even be considered as an alternative to tricuspid regurgitation-derived PAP systolic when tricuspid regurgitation is nonrecordable. A proposed method to derive systolic PAP should be used while screening the patients at risk for pulmonary hypertension, monitoring the disease progression and the effect of treatment.

Adult↗

PubMed2005

Anaesthesia management for pulmonary endarterectomy.

PURPOSE OF REVIEW: Options for the surgical treatment of chronic thromboembolic pulmonary hypertension are either lung transplantation or pulmonary endarterectomy. Pulmonary endarterectomy is considered permanently curative and the treatment of choice. The procedure dramatically improves functional status and provides an excellent immediate and long-term survival, much better than transplantation. Pulmonary endarterectomy, until recently performed in only a few highly specialized centres, is now spreading worldwide with good results. This review will focus on the understanding of the pathophysiology of the disease and on recent advances in assessment and treatment strategies. RECENT FINDINGS: Recent data reinforce the thromboembolic nature of chronic thromboembolic pulmonary hypertension, and have shown that the disorder is more common than was thought and remains underdiagnosed. There has recently been a remarkable surge in the understanding of the mechanisms involved in the pathogenesis of pulmonary hypertension. Advances in diagnosis, surgical techniques, preoperative treatment, and perioperative management have improved the prognosis of this debilitating disease. New information about pretreatment and medical treatment with prostanoids and endothelin receptor antagonists is now available. SUMMARY: Pulmonary endarterectomy can be successfully performed in selected centres using a multidisciplinary approach involving the specialities of surgery, pulmonary medicine, cardiology, radiology, anaesthesiology and critical care medicine. The largest risk factor remains the degree of operability related to a high pulmonary vascular resistance caused by permanent changes in the pulmonary vascular bed. Early operation is now recommended to prevent these irreversible changes. Further investigations are warranted to establish the role of new drugs in surgical patients with chronic thromboembolic pulmonary hypertension.

Journal Article↗

PubMed2005

Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Pulmonary thromboendarterectomy (PTE) is a surgical procedure which is considered the only effective and potentially curative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is a rare outcome from pulmonary emboli and, when left untreated, will result in right ventricular failure and death. METHODS: From June 1999 to November 2003, 40 of these procedures were performed in our institution. Emphasis is placed on multidisciplinarity and cooperation between different medical and surgical disciplines. Perfusion management consists of myocardial and cerebral protection, deep hypothermia with multiple periods of circulatory arrest, reperfusion at hypothermia, hemofiltration and cellsaving techniques. RESULTS: Hemodynamic improvement occurs immediately post operation. Mean pulmonary artery pressure decreased from 50 +/- 11 to 38 +/- 10 mmHg, pulmonary vascular resistance from 1246+482 to 515 +/- 294 dynes s/cm5 and cardiac index increased from 1.54 +/- 0.54 to 2.63 +/- 0.75 L/min per m2. Pump runs had an average duration of 187 +/- 29 min, circulatory arrest time was 29 +/- 11 min and crossclamp time 36 +/- 14 min. Extracorporeal membrane oxygenation can be an ultimate treatment for specific postoperative problems like persistent pulmonary hypertension and/or reperfusion pulmonary edema.

Chronic Disease↗

PubMed2004

Prostanoid therapy for pulmonary arterial hypertension.

Prostanoids have played a prominent role in the treatment of pulmonary arterial hypertension (PAH). Several compounds and methods of administration have been studied: chronic intravenously infused epoprostenol, chronic subcutaneously infused treprostinil, inhaled iloprost, and oral beraprost. Chronic intravenous epoprostenol therapy has had a substantial impact on the clinical management of patients with severe PAH. It improves exercise capacity, hemodynamics, and survival in patients with idiopathic pulmonary arterial hypertension (IPAH). It also improves exercise capacity and hemodynamics in patients with PAH occurring in association with scleroderma. The complexity of epoprostenol therapy (chronic indwelling catheters, reconstitution of the drug, operation of the infusion pump, and others) has led to attempts to develop other prostanoids with simpler modes of delivery. Treprostinil, a stable prostacyclin analogue with a half-life of 3 h, has been developed for subcutaneous delivery. It has beneficial effects on exercise and hemodynamics, which depend somewhat on the dose achieved. This, in turn, is determined by the patient's ability to tolerate the drug's side effects, including pain and erythema at the infusion site. Inhaled iloprost therapy may provide selectivity of the hemodynamic effects to the lung vasculature, thus avoiding systemic side effects. In a randomized and controlled trial, iloprost resulted in improvement in a combined end point incorporating the New York Heart Association functional class, 6-min walk test, and deterioration or death. Beraprost is the first orally active prostacyclin analogue. In the first of two randomized controlled trials, beraprost increased exercise capacity in patients with IPAH, with no significant changes in subjects with associated conditions. Hemodynamics did not change significantly, and no difference in survival was detected between the two treatment groups. The second study showed that beraprost-treated patients had less disease progression at six months and confirmed the results of the previous trial. However, this improvement was no longer present at 9 or 12 months. In conclusion, though treatment with prostanoids is complicated by their generally short half-lives and complicated drug delivery systems, they continue to play an important role in the treatment of PAH.

Antihypertensive Agents↗

PubMed2003

Differential changes in regional right ventricular function before and after a bilateral lung transplantation: an ultrasonic strain and strain rate study.

The evaluation of regional right ventricular function by ultrasound remains a challenge. This case report demonstrates the potential value of the new cardiac deformation indices, strain and strain rate imaging, in determining the differing regional abnormalities in longitudinal right ventricular function before and after bilateral lung transplantation. These indices were measured in a patient with severe right ventricular dysfunction as a result of primary pulmonary hypertension.

Adult↗

PubMed2002

The use of ECG and respiratory triggering to improve the sensitivity of oxygen-enhanced proton MRI of lung ventilation.

Changes in lung signal between normal breathing and breathing pure oxygen is the basis for oxygen-enhanced ventilation MRI. An optimal technique guarantees a significant response to pure oxygen in well-ventilated lung tissue. To improve the sensitivity, we investigated the effect of ECG and respiratory triggering. Centric reordered single-shot rapid acquisition relaxation enhancement sequences (TE 4.2 ms, echo spacing 4.2 ms, bandwidth 650 Hz/pixel), with an inversion recovery preparation pulse (TI 700 ms), were used. Series of 20 measurements were performed with and without ECG and respiratory triggering in five young volunteers. Subsequently, series of 100 images were acquired during breathing normal air and pure oxygen (as "stimulus"). Ventilation maps showed by means of the z-score how far the response deviates from the signal intensities during the normal air condition. The standard deviation of the lung signal intensities was lowest for the cardiac-triggered series. In the ventilation maps, on the other hand, signal changes were statistically more significant in the respiratory than in the cardiac-triggered series. The average z-scores in the right (left) cranial part of the lung were 12.4 (13.0) and 9.2 (9.7) for respiratory and ECG-triggered acquisitions. We propose to use respiratory triggering as a means to improve the sensitivity of MR ventilation studies.

Adult↗

PubMed2002

Inhaled iloprost for severe pulmonary hypertension.

BACKGROUND: Uncontrolled studies suggested that aerosolized iloprost, a stable analogue of prostacyclin, causes selective pulmonary vasodilatation and improves hemodynamics and exercise capacity in patients with pulmonary hypertension. METHODS: We compared repeated daily inhalations of 2.5 or 5.0 microg of iloprost (six or nine times per day; median inhaled dose, 30 microg per day) with inhalation of placebo. A total of 203 patients with selected forms of severe pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (New York Heart Association [NYHA] functional class III or IV) were included. The primary end point was met if, after week 12, the NYHA class and distance walked in six minutes were improved by at least one class and at least 10 percent, respectively, in the absence of clinical deterioration according to predefined criteria and death. RESULTS: The combined clinical end point was met by 16.8 percent of the patients receiving iloprost, as compared with 4.9 percent of the patients receiving placebo (P=0.007). There were increases in the distance walked in six minutes of 36.4 m in the iloprost group as a whole (P=0.004) and of 58.8 m in the subgroup of patients with primary pulmonary hypertension. Overall, 4.0 percent of patients in the iloprost group (including one who died) and 13.7 percent of those in the placebo group (including four who died) did not complete the study (P=0.024); the most common reason for withdrawal was clinical deterioration. As compared with base-line values, hemodynamic values were significantly improved at 12 weeks when measured after iloprost inhalation (P<0.001), were largely unchanged when measured before iloprost inhalation, and were significantly worse in the placebo group. Further significant beneficial effects of iloprost treatment included an improvement in the NYHA class (P=0.03), dyspnea (P=0.015), and quality of life (P=0.026). Syncope occurred with similar frequency in the two groups but was more frequently rated as serious in the iloprost group, although this adverse effect was not associated with clinical deterioration. CONCLUSIONS: Inhaled iloprost is an effective therapy for patients with severe pulmonary hypertension.

Administration, Inhalation↗

PubMed2002

Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: The purpose of this study was to assess the efficacy and safety of beraprost sodium, an orally active prostacyclin analogue, in New York Heart Association (NYHA) functional class II and III patients with pulmonary arterial hypertension (PAH). BACKGROUND: Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous infusion of prostacyclin has been proven effective. However, this treatment is associated with serious complications arising from the complex delivery system. METHODS: In this double-blind, placebo-controlled study, 130 patients with PAH were randomized to the maximal tolerated dose of beraprost (median dose 80 microg four times a day) or to placebo for 12 weeks. The primary end point was the change in exercise capacity assessed by the 6-min walk test. Secondary end points included changes in Borg dyspnea index, cardiopulmonary hemodynamics and NYHA functional class. RESULTS: Patients treated with beraprost improved exercise capacity and symptoms. The difference between treatment groups in the mean change of 6-min walking distance at week 12 was 25.1 m (95% confidence interval [CI]: 1.8 to 48.3, p = 0.036). The difference in the mean change of Borg dyspnea index was -0.94 (95% CI: -1.63 to -0.24, p = 0.009). In the sub-group of patients with primary pulmonary hypertension, the difference in the mean change of 6-min walking distance was 46.1 m (95% CI: 3.0 to 89.3, p = 0.035). Cardiopulmonary hemodynamics and NYHA functional class had no statistically significant changes. Drug-related adverse events were common in the titration phase and decreased in the maintenance period. CONCLUSIONS: Beraprost improves exercise capacity and symptoms in NYHA functional class II and III patients with PAH and, in particular, in those with primary pulmonary hypertension.

Administration, Oral↗

PubMed2002

Combined liver and (heart-)lung transplantation in liver transplant candidates with refractory portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension (PPHT) has a prevalence of 5-10% in liver transplantation (LiTx) candidates. Mild PPHT is reversible with LiTx, but more severe PPHT is a contraindication to LiTx given the high intraoperative mortality due to heart failure. Prostacyclin can reduce PPHT to a level at which LiTx can be performed. In patients refractory to that treatment, combined (heart-)lung-LiTx is the only life-saving option. METHODS: We report two cases of (heart-)lung-LiTx in patients with refractory severe PPHT. RESULTS: Patient 1, a 52-year-old female with viral cirrhosis and severe refractory PPHT, received a double-lung Tx followed by LiTx. After liver reperfusion, fatal heart failure occurred. Patient 2, a 42-year-old male with viral hepatitis and congenital liver fibrosis, also suffered from severe refractory PPHT. He successfully received an en bloc heart-lung Tx followed by LiTx. The rationale to replace the heart was an anticipated risk of intraoperative right heart failure after liver reperfusion and the technical ease of heart-lung versus double-lung Tx. CONCLUSION: Severe refractory PPHT is a fatal condition seen as a contraindication to LiTx. This condition can be treated by replacing thoracal organs in addition to the liver. Additional evidence via development of a registry is required to further support application of liver-(heart-)lung Tx in patients with severe refractory PPHT.

Adult↗