Pascal Lacombe

Bevacizumab in Patients With Hereditary Hemorrhagic Telangiectasia and Severe Hepatic Vascular Malformations and High Cardiac Output

CONTEXT The only treatment available to restore normal cardiac output in patients with hereditary hemorrhagic telangiectasia (HHT) and cardiac failure is liver transplant. Anti-vascular endothelial growth factor treatments such as bevacizumab may be an effective treatment. OBJECTIVES To test the efficacy of bevacizumab in reducing high cardiac output in severe hepatic forms of HHT and to assess improvement in epistaxis duration and quality of life. DESIGN, SETTING, AND PATIENTS Single-center, phase 2 trial with national recruitment from the French HHT Network. Patients were 18 to 70 years old and had confirmed HHT, severe liver involvement, and a high cardiac index related to HHT. INTERVENTION Bevacizumab, 5 mg per kg, every 14 days for a total of 6 injections. The total duration of the treatment was 2.5 months; patients were followed up for 6 months after the beginning of the treatment. MAIN OUTCOME MEASURE Decrease in cardiac output at 3 months after the first injection, evaluated by echocardiography. RESULTS A total of 25 patients were included between March 2009 and November 2010. Of the 24 patients who had echocardiograms available for reread, there was a response in 20 of 24 patients with normalization of cardiac index (complete response [CR]) in 3 of 24, partial response (PR) in 17 of 24, and no response in 4 cases. Median cardiac index at beginning of the treatment was 5.05 L/min/m(2) (range, 4.1-6.2) and significantly decreased at 3 months after the beginning of the treatment with a median cardiac index of 4.2 L/min/m(2) (range, 2.9-5.2; P < .001). Median cardiac index at 6 months was significantly lower than before treatment (4.1 L/min/m(2); range, 3.0-5.1). Among 23 patients with available data at 6 months, we observed CR in 5 cases, PR in 15 cases, and no response in 3 cases. Mean duration of epistaxis, which was 221 minutes per month (range, 0-947) at inclusion, had significantly decreased at 3 months (134 minutes; range, 0-656) and 6 months (43 minutes; range, 0-310) (P = .008). Quality of life had significantly improved. The most severe adverse events were 2 cases of grade 3 systemic hypertension, which were successfully treated. CONCLUSION In this preliminary study of patients with HHT associated with severe hepatic vascular malformations and high cardiac output, administration of bevacizumab was associated with a decrease in cardiac output and reduced duration and number of episodes of epistaxis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00843440.

Diagnosis and treatment of pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: An overview.

Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomic dominant disorder, which is characterized by the development of multiple arteriovenous malformations in either the skin, mucous membranes, and/or visceral organs. Pulmonary arteriovenous malformations (PAVMs) may either rupture, and lead to life-threatening hemoptysis/hemothorax or be responsible for a right-to-left shunting leading to paradoxical embolism, causing stroke or cerebral abscess. PAVMs patients should systematically be screened as the spontaneous complication rate is high, by reaching almost 50%. Neurological complications rate is considerably higher in patients presenting with diffuse pulmonary involvement. PAVM diagnosis is mainly based upon transthoracic contrast echocardiography and CT scanner examination. The latter also allows the planification of treatments to adopt, which consists of percutaneous embolization, having replaced surgery in most of the cases. The anchor technique consists of percutaneous coil embolization of the afferent pulmonary arteries of the PAVM, by firstly placing a coil into a small afferent arterial branch closely upstream the PAVM. Enhanced contrast CT scanner is the key follow-up examination that depicts the PAVM enlargement, indicating the various mechanisms of PAVM reperfusion. When performed by experienced operators as the prime treatment, percutaneous embolization of PAVMs, is a safe, efficient and sustained therapy in the great majority of HHT patients.

Motion artifacts of the aorta simulating aortic dissection on spiral CT.

PURPOSE Motion artifacts of the ascending aorta may impair image quality and simulate an intimal flap or a false channel. The purpose of this study is to evaluate the prevalence, amplitude, and extent of motion artifacts of the aorta in spiral CT and to specify the effects of acquisition and reconstruction parameters on these artifacts. METHOD One hundred seventy-one thoracic spiral CT examinations were retrospectively analyzed by two reviewers. The analysis sought to determine the presence, location, amplitude, and extent of artifacts of the ascending aorta. RESULTS Aortic artifacts were detected on spiral CT in 57% of cases. The mean amplitude and mean extent were 4+/-4 and 6+/-7 mm, respectively. Artifacts in the ascending aorta were significantly higher with the 360 degrees linear interpolation (LI) algorithm than with the 180 degrees LI algorithm. CONCLUSION The prevalence of motion artifacts on spiral CT is higher in this study than the reported prevalence in incremental CT. However, this higher prevalence is significantly reduced when the 180 degrees LI algorithm is used.

Diffuse Pulmonary Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia: Long-term Results of Embolization According to the Extent of Lung Involvement

OBJECTIVES To review the safety of embolization in patients affected with hereditary hemorrhagic telangiectasia (HHT) presenting with diffuse pulmonary arteriovenous malformations (PAVMs). To correlate the initial presentation and long-term results of embolization according to the distribution of PAVMs. MATERIALS AND METHODS All consecutively treated patients were divided into three groups, according to the involvement of every subsegmental pulmonary artery (group 1), segmental artery (group 2), or both (group 3) of at least one lobe. Age, sex, initial clinical presentation, and Pao(2) were recorded before embolization. Per and postprocedural complications were carefully recorded. Clinical outcome and imaging follow-up were obtained at 6 months and annually thereafter. RESULTS Thirty-nine patients (31 women, 8 men; mean age, 35 years), all of them with bilateral lung involvement, were treated. Group 1 consisted of 8, group 2 of 17, and group 3 of 14 patients. Dyspnea was present in 35 of the patients (90%) and cyanosis in 17 patients (44%). Preembolization Pao(2) was different between groups 1 (52.6 +/- 11.6 mm Hg) and 3 (70.7 +/- 14.1 mm Hg). Neurologic events were more frequently reported before treatment in group 1 (62.5%) than in group 2 (35%) or in group 3 (43%). Eighty percent of patients reported improvement in their dyspnea after embolization. Pao(2) levels improved more in group 2 than in groups 1 and 3. Eight ischemic or infectious complications occurred in 4 patients (10%) due to reperfusion of embolized PAVMs or enlargement of non-embolized PAVMs. Complete and partial treatment success was reported using CT scanning in 59% and 38% of cases, respectively. CONCLUSION Dyspnea and paradoxical embolism are frequently encountered in HHT patients with diffuse PAVMs. Prevention of complications and improvement of dyspnea can be achieved after successful embolization in most patients. Better improvement of Pao(2) can be achieved in group 2.

Prevalence, Characteristics, and Outcomes of Patients Presenting With Cardiogenic Unilateral Pulmonary Edema

Background— Cardiogenic unilateral pulmonary edema (UPE) is a rare entity, frequently leading to initial misdiagnosis. We sought to assess the prevalence of UPE and to determine its impact on prognosis compared with bilateral pulmonary edema. Methods and Results— We studied the characteristics and outcomes of patients admitted to our institution for cardiogenic pulmonary edema during an 8-year period. The study population included 869 consecutive patients. The prevalence of UPE was 2.1%: 16 right-sided UPE (89%) and 2 left-sided UPE (11%). In patients with UPE, blood pressure was significantly lower (P≤0.01), whereas noninvasive or invasive ventilation and catecholamines were used more frequently (P=0.0004 and P<0.0001, respectively). The prevalence of severe mitral regurgitation in patients with bilateral pulmonary edema and UPE was 6% and 100%, respectively (P<0.0001). In patients with UPE, use of antibiotic therapy and delay in treatment were significantly higher (P<0.0001 and P=0.003, respectively). In-hospital mortality was 9%: 39% for UPE versus 8% for bilateral pulmonary edema (odds ratio, 6.9; 95% confidence interval, 2.6 to 18; P<0.001). In multivariate analysis, unilateral location of pulmonary edema was independently related to death whatever the model used (adjusted odds ratio, 6.5; 95% confidence interval, 1.3 to 32; P=0.021 for model A; and adjusted odds ratio, 6.8; 95% confidence interval, 1.1 to 41; P=0.037 for model B). Conclusions— Unilateral pulmonary edema represented 2.1% of cardiogenic pulmonary edema in our study, usually appeared as an opacity involving the right lung, and was always associated with severe mitral regurgitation. Unilateral pulmonary edema is related to an independent increased risk of mortality and should be promptly recognized to avoid delays in treatment.

Usefulness of contrast echocardiography for assessment of intracardiac masses

BACKGROUND Conventional echocardiography is not a reliable method for characterizing tissue patterns of intracardiac masses. AIMS To assess the ability of contrast echocardiography to characterize intracardiac masses. METHODS Thirty-one consecutive patients with an intracardiac mass were included in this prospective study. All patients underwent conventional and contrast echocardiographic examinations. Analysis of characteristics by contrast agent allowed classification of intracardiac masses as follows: complete lack of enhancement, suggesting thrombus; partial and/or incomplete enhancement, suggesting myxoma; complete enhancement, suggesting intracardiac tumor. Tissue characteristics of intracardiac masses were also analyzed using at least one of the following techniques: cardiac magnetic resonance, pathology of intracardiac mass and/or mass resolved after anticoagulation during follow-up. RESULTS Using contrast echocardiography, an accurate diagnosis was made in all patients by an experienced investigator and in all patients except one (97%), by a physician trainee (p=0.31). Among patients with a history of tumor, echocardiography allowed accurate diagnosis of the nature of the mass in all patients; 50% of these patients presented with a secondary cardiac tumor and the others had a thrombus. Of the 14patients with a thrombus located in the left ventricle, 12 (86%) presented with left ventricular motion abnormalities using conventional echocardiography, whereas wall motion abnormalities were observed in all 14patients (100%) using contrast agent. In these patients, 91 and 99% of left ventricular segments were well visualized using conventional and contrast echocardiography, respectively (p<0.0001). CONCLUSIONS Contrast echocardiography may be useful for the tissue characterization of intracardiac masses.

Triage Patients with Suspected Pulmonary Embolism in the Emergency Department Using a Portable Ultrasound Device

The diagnosis of pulmonary embolism (PE) is difficult, despite validated diagnostic models. We sought to determine the value of a portable ultrasound device for triage of patients with suspected PE referred to the emergency department, using simplified echo criteria. We prospectively studied 103 consecutive patients with suspected PE, referred to our emergency department. After D‐dimer screening, 76 patients were prospectively enrolled in this ultrasound study and underwent helical chest tomography, transthoracic echocardiography, and venous ultrasonography. Among patients with PE (n = 31), a right ventricular dilation was detected in 17 patients (55%), a direct visualization of clot in the lower limbs was present in 18 patients (58%), and 8 patients (26%) had both right ventricular dilation and deep venous thrombosis. The sensitivity and specificity of a combined ultrasound strategy using echocardiography and venous ultrasonography were respectively 87% (95% confidence interval 74% to 96%), and 69% (95% confidence interval 53% to 82%). The sensitivity of this combined strategy was significantly improved as compared to venous ultrasonography alone (P = 0.01) or echocardiography alone (P = 0.005). In patients with dyspnea or with high clinical probability of PE, this combined strategy was particularly relevant with high sensitivities (respectively 94% and 100%). Echocardiography combined with venous ultrasonography using a portable ultrasound device is a reliable method for screening patients with suspected PE referred to an emergency department, especially in patients with dyspnea or with high clinical probability.

Occlusive arterial disease of abdominal aorta and lower extremities Comparison of helical CT angiography with transcatheter angiography

The purpose of this study was to evaluate helical CT angiography in the assessment of occlusive arterial disease of abdominal aorta and the lower extremities. Sixteen patients underwent both transcatheter angiography and helical CT. Helical CT was inconclusive in 6.2% of segments whereas angiography was inconclusive in 5%. The overall sensitivity of helical CT was 91% and specificity 93%. Segmental analysis found a sensitivity of 43% in infrapopliteal arteries, and a specificity of 86%.

Value of Tissue Doppler Imaging to Predict Left Ventricular Filling Pressure in Patients with Coronary Artery Disease

Assessment of left ventricular (LV) diastolic filling pressure provides important information on the hemodynamic status in the general population. The aim of our study was to investigate the reliability of tissue Doppler imaging (TDI) in estimating left ventricular filling pressure in patients with coronary artery disease (CAD). We prospectively studied 32 consecutive CAD‐patients, mean age 64 ± 12 years, in sinus rhythm. All patients underwent cardiac catheterization and echocardiography within the same hour. Catheterization investigated pre‐A‐wave pressure (preA) and LV ejection fraction (LVEF). Echocardiographic LVEF was calculated using wall motion indexes (WMI) with segmental division of LV wall. The following Doppler parameters were assessed: (1) PW Doppler signals from the mitral inflow (E), (2) PW TDI of the mitral annulus (E′), thus allowing to obtain the mitral inflow to annulus ratio (E/E′). The best correlation between invasive and echocardiographic LVEF was observed using WMI (r = 0.91). The correlations between preA and E, E′, and E/E′ were significant (r = 0.36, r = 0.38, and r = 0.60, respectively). In patients with LVEF >50%, no correlation between E/E′ and preA was found (r = 0.18, P = 0.44), whereas with LVEF <50%, this correlation was strong (r = 0.76, P < 0.001). In patients with myocardial infarction, the correlation between E/E′ and preA was significant whatever the localization of myocardial infarction (r > 0.71, P < 0.05). ROC curve analysis identified an E/E′>9 to be the best cut‐off value related to preA > 15 mmHg. We conclude that the mitral inflow‐to‐annulus ratio is a reliable method in CAD patients and allows determination of LV filling pressure when LVEF <50%. (ECHOCARDIOGRAPHY, Volume 21, February 2004)

Volumetric quantification of coronary artery calcifications using dual-slice spiral CT scanner : Improved Reproducibility of measurements with 180° linear interpolation algorithm

Purpose The purpose of this work was to determine the reproducibility of coronary total calcium score (TCS) with dual-slice helical CT and compare three acquisition protocols. Method Fifty patients (59 ± 10 years old) underwent dual-slice helical CT (collimation = 2 × 2.5 mm) and coronary angiography. Two successive scans were performed, resulting in three sets of images: pitch = 1, 360° linear interpolation (LI) (A360); pitch = 1, 180° LI (A180); and pitch = 1.5, 180° LI (B180). TCS values, calculated using a volumetric method with a threshold of 90 HU, were compared, and the interscan variation was determined. Diagnostic performances were compared with receiver operating characteristic curves. Results Protocol A360 provided significantly lower TCS than protocols A180 and B180 (p < 0.0001). No statistical difference was seen between A180 and B180, which provided the lowest interscan variation (40 ± 58%). However, no significant clinical impact of the observed interscan variations was found. Conclusion Reproducibility of TCS with dual-slice helical CT is improved by the 180 LI algorithm. However, dual-slice helical CT is not sufficiently reproducible to allow serial quantification of TCS over time.