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Purpose: Trastuzumab is the most widely prescribed anti-HER2 humanized monoclonal antibody. Cardiac toxicity is the only limiting toxicity of trastuzumab and it is of particular concern in patients with complete response, since the drug needs to be stopped, with a risk of disease relapse. To date, no pharmacological data on trastuzumab cardiotoxicity in patients have been made available. Here, we provide proof of concept, demonstrating that it was possible to prevent trastuzumab-induced cardiotoxicity by modifying the drug administration schedule., Methods: In this paper, we report the case of a patient with metastatic breast cancer responding to trastuzumab, who developed severe cardiac toxicity twice using a 3-weekly regimen. Considering preclinical pharmacological data on trastuzumab cardiotoxicity, we hypothesized that a weekly schedule of trastuzumab with lower peaks of serum concentration could be safe while remaining efficient. With the patient's consent, we started a weekly combination of carboplatin (AUC2) and trastuzumab (2 mg/kg) with close monitoring of trastuzumab concentrations., Results: We successfully controlled the disease for an additional 6 months with relevant trough concentrations of trastuzumab of around 50 mg/L. Another important aspect is that, with this weekly schedule, we observed no cardiac toxicity, and the left ventricular ejection fraction remained stabilized, at over 50%., Conclusions: Trastuzumab is the most widely prescribed anti-HER2 monoclonal antibody for the treatment of HER2 metastatic breast cancer, and it is the only drug that has been approved for the treatment of localized HER2 breast cancer, 1-year treatment being required after surgery. In case of cardiac toxicity, particularly in women over 60 years of age, a weekly regimen with lower peaks of concentration could be an alternative to the standard 3-weekly regimen.

Aim of the Study: In the setting of ischemic stroke, the place of transesophageal echocardiography (TEE) is still matter of debate. The aim of the study is to evaluate the therapeutic impact provided by TEE and to characterize patients in whom TEE is warranted., Patients and Method: Three hundred and fifty-nine consecutive patients were included in the study. "Decisive TEE" (DTEE) was defined by echographic findings resulting in a change of treatment, whereas "informative TEE" (ITEE) was defined by TEE revealing a potential cardiac or aortic source of embolism., Results: Three hundred and forty-one patients underwent TEE. Twenty-eight patients (8.2%) had DTEE and 184 (53.9%) had ITEE. DTEE were as follows: thrombus in the left atrial appendage in 6 patients, complex aortic plaques in 10 patients, patent foramen ovale (PFO) associated with atrial septal aneurism (ASA) and an important right to left shunt (3 patients), FOP associated with ASA and lower limb phlebitis (1 patient), 4 cases of endocarditis and 4 patients with intense spontaneous echo contrast in the left atrium. In most cases of DTEE (67.8%), the patient was given anticoagulation drugs. Left atrial dilatation (P=0.005) and multivessel territory stroke (P=0.018) were statistically predictive of DTEE., Conclusions: In the setting of ischemic stroke, TEE provides important additional informations, but modifies therapeutic strategy in less than 10% of cases. Multivessel territory stroke, and left atrial dilatation were predictive of DTEE., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The purpose of this study, performed in 80 patients with aortic valve stenosis, was to find out whether continuous wave doppler ultrasound was reliable in assessing the severity of the stenosis. Maximum mean and instantaneous transaortic pressure gradients obtained by continuous wave doppler were compared with maximum mean instantaneous and peak to peak gradients simultaneously obtained by cardiac catheterization. 35 patients who underwent aortic valve dilation were explored beforehand and afterwards, which brings up to 115 the total number of gradient comparisons. There was a correlation between maximum instantaneous gradient at doppler and peak to peak gradient (r = 0.62, n = 115, e = 22.5 mmHg, p less than 0.001). A similar correlation was found between maximum instantaneous gradients at doppler and haemodynamics (r = 0.64, n = 80, e = 24.5 mmHg), but correlation between mean gradients was weaker (r = 0.57, n = 80, e = 17.7 mmHg). Maximum and mean instantaneous gradients are underestimated by the doppler method. After exclusion of imperfect doppler curves, correlations were better, notably as regards mean gradients (r = 0.80, n = 18, e = 11.9 mmHg). There was a closer correlation between doppler maximum instantaneous gradients and haemodynamic peak to peak gradients in patients without aortic regurgitation (r = 0.71, n = 45, e = 17.2 mmHg) than in patients with aortic regurgitation (r = 0.54, n = 70, e = 24.3 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler sonography permits to diagnose the gravity of valvular aortic stenosis if absolute conditions of reliability of the method are respected. The Doppler examination must be performed by a physician particularly familiar with this technique because it is a difficult examination. Systematic trial of the 5 possible approaches of the aortic orifice must be required: apical, left and right parasternal, substernal and sub-xyphoid approaches. Only velocity curves with a well defined contour must be retained and the concordance of the maximal velocities obtained by apical and parasternal approaches is in favor of a good alignment of the ultrasound beam on the aortic flow. It must be remembered that any sub-aortic obstacle or severe aortic insufficiency simulates an aortic stenosis on a continuous Doppler and that it is necessary to resort to the pulsated Doppler to rectify the diagnosis: acceleration of the flow occurs therefore in the flush chamber of the left ventricle and not at the level of the sigmoid orifice. We will remember that the Doppler does not provide the peak to peak gradient seen in hemodynamics but the maximal instant gradient which is always higher than the first one, and more especially as the aortic stenosis is more moderate. The best criteria of gravity of an aortic stenosis remain the mean gradient and the valvular area: the mean gradient is easily deduced from the quadratic transformation of the Doppler velocity curve and from a simple planimetry. The valvular area is obtained by applying the continuity equation which permits to get rid nicely of the cardiac output but still requires more validation before becoming part of the routine.

The respective diagnostic values of M mode and 2D echocardiography and pulsed and continuous wave Doppler were assessed in bioprosthetic valve dysfunction. The results of the ultrasonic investigations were compared with the operative findings and anatomo pathological appearances in 56 cases of dysfunction. Only cases with surgical confirmation were included. Doppler examinations were carried out in 13 cases. Echocardiographic imaging alone cannot resolve all the diagnostic problems posed: specific signs are rare and were only observed in one out of 7 cases of periprosthetic leak, 7 out of 10 cases of valvular stenosis and 20 out of 36 cases (55 per cent) of valve tear. In cases of valve tear, 2D echocardiography was falsely normal in 15 per cent of cases and gave equivocal results in 30 per cent of cases because it was not possible to visualise the three cusps of the bioprostheses. Doppler echocardiography does not have the same limitations and gives an immediate and accurate assessment of valve function. It is particularly useful for the diagnosis of stenosis and valve tear in which the diagnostic specificity and sensitivity attain 100 per cent (exact diagnosis in all 11 cases of valve tear). At present, continuous wave Doppler seems to be the most reliable diagnostic tool for qualitative and quantitative assessment of primary degeneration of valvular prostheses.

The clinical story and the results of radiological and angiocardiographic investigations in 2 patients with proven mitral valve prolapse and cerebral ischemia are reported. Significant risk factors for stroke other than mitral valve prolapse were lacking. Cerebral angiography showed in one case a distal occlusion suggesting embolic brain lesion and was normal in the other case. This report suggests: 1) that mitral valve prolapse is a real risk factor for stroke in young people; 2) that two-dimensional echocardiography or angiocardiography are valuable investigations in young patients with cerebral ischemia, when clinical or electrocardiographical findings of cardiopathy are present.

In order to assess the validity of the continuity equation applied to doppler ultrasound in the evaluation of stenotic aortic valve areas, the authors have compared the results obtained in 24 patients examined by catheterization and doppler-echocardiography. In addition, 10 patients who underwent aortic dilatation also had both types of examination, which brings up to 34 the number of comparisons. In haemodynamics, the Gorlin formula was taken as reference for valve area measurement. The doppler-echocardiographic examination, performed 48 hours before, and sometimes after catheterization, recorded sub- and trans-stenotic pressures and outflow tract diameter for application of the continuity equation. Aortic valve areas calculated from doppler data on mean velocities correlated well with areas calculated from haemodynamic data (r = 0.88, p less than 0.001, e = 14 mm2, n = 34). Correlation was even closer when maximum velocities were used (r = 0.96, p less than 0.001, e = 8 mm2, n = 34). When only tight aortic stenoses with a less than 0.75 cm2 area were considered, the correlation remained very good (r = 0.87, p less than 0.001, e = 6 mm2, n = 34). This study therefore demonstrates the reliability of the continuity equation and of the simplified method using maximum sub- and trans-stenotic pressures without having recourse to planimetry. The accuracy of the method is dependent upon 3 parameters: 1. A maximum velocity jet must be obtained, which in turn depends on the investigator's experience and on the sensitivity of the equipment. 2. The velocity recorded by pulsed doppler ultrasound must be "representative" of flow in the outflow tract.(ABSTRACT TRUNCATED AT 250 WORDS)

The authors study the sensitivity, the specificity and the predicting value of Frank's sign (presence of a groove at the level of the earlobe) on a group of 172 patients undergoing a clinical examination, an EKG at rest and effort, and a selective coronary arteriogram for suspicion of coronary disease. The criteria retained for the diagnosis of coronary disease is the presence of stenosis superior or equal to 75 p. cent in one of the three main coronary vascular trunks. Statistical studies using the CHI 2 test reveal a highly significant association between Frank's sign and coronary disease (p less than 0.001). The sensitivity of Frank's sign reaches 75 p. cent, its specificity 57.5 p. cent and its positive predicting value 80.3 p. cent. The predicting value is a function of the sex: it is a great deal lower in women (50 p. cent) than in men (84.7 p. cent). The prevalence of Frank's sign increases progressively with age: 42 p. cent in the 30-39 age group and 75.8 p. cent in the 60-69 age group. The predicting value remains high however beyond 60 years: predicting value of 77 p. cent. Frank's sign is correlated neither with the gravity of the coronary disease, nor the duration of the angina, nor with any of the risk factors studied here: tobacco, hypercholesterolemia, arterial hypertension, diabetes, obesity. Frank's sign is therefore considered as a marker of the coronary disease, independent of risk factors but frequently associated with them. If its absence does not permit in any way to exclude the diagnosis of coronary disease, its presence corresponds in three quarters of the cases to an established coronary disease within a symptomatic population.(ABSTRACT TRUNCATED AT 250 WORDS)

The positive diagnosis of tricuspid insufficiency is simple: it consists in demonstrating in pulsated Doppler, the presence of retro-tricuspid systolic turbulence in the right atrium. The best views for this diagnosis are the 4 cavities apical section and the mitro-tricuspid section. This criterion appears to be extremely specific and only exceptional left ventricle-right atrium communications are capable to also generate right intra-atrial turbulences. In our experiment the sensitivity is close to 93%. The advantage of the continuous Doppler is to permit the measurement of the maximal velocity of the regurgitating tricuspid flow and the evaluation of the right ventricular pressure and the pulmonary artery pressure. The best criteria of gravity of tricuspid insufficiency are: the acoustical and graphic intensity of the Doppler signal, the spatial extension of systolic turbulences within the right atrium, the velocity of the anterograde tricuspid flow which reaches and exceeds lm/sec in severe tricuspid insufficiencies, and the laminar nature of the regurgitating flow, a sign of great value in favor of a massive tricuspid insufficiency. The color Doppler represents the future.

In order to evaluate the severity of aortic valve regurgitation (AVR) by means of simple criteria, we compared the feasibility and reliability of two methods: (1) pulsed doppler ultrasound suprasternal recording in the aortic sinus area, with calculation of the regurgitation fraction by planimetry of the systolic and diastolic curves, and with measurement of end-diastolic velocity, or end-diastolic doppler effect (EDDE); this was done in 114 subjects (84 patients with AVR and 30 controls); (2) continuous wave doppler ultrasound apical recording of the left intraventricular jet, with measurement of the velocity decrease slope (S) and of the velocity half-decrease time (T 1/2); this was done in 46 patients with AVR. Doppler results were compared with Seller's angiographic classification of AVR in 4 grades. Planimetry could be performed in only 41% of patients in this series. This measurement seems to be feasible only when perfect recording of an increased systolic flow (peak velocity higher than 1.2 m/s) can be performed, which is usually limited to cases with major regurgitation. EDDE was easier to record (84/84 patients). When above 5 cm/s it is a good reflection of AVR severity, and when above 20 cm/s it indicates a major AVR (3/4 or 4/4 at angiography), with an 81% sensitivity and a 91% specificity. Continuous wave doppler ultrasound apical recording could be used in 80% of the cases (37/46 patients). With this method, a more than 3 m/s slope is a highly specific (8/8) but not very sensitive (8/13) sign of major AVR. A T 1/2 value lower than 650 ms is a specific (12/12) and sensitive (12/13) sign of severe AVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute digitalis intoxication is infrequent and severe. The mortality rate is between 15 and 20 per cent. Its treatment has been greatly improved with the appearance, in 1976, of a specific serotherapy: Fab fragments of antidigoxin antibodies. The clinical experiment reported in the literature relates to approximately one hundred cases and establishes that this therapy has a practically constant and non dangerous efficacy. The lack of availability of these fragments Fab represents presently the only obstacle to the development of this treatment, but the use of monoclonal antibodies, already available experimentally, should, in the future, circumvent this last hurdle.

Fifty patients underwent a 24-hour Holter system recording immediately after successful coronary angioplasty. Only those patients who had been "successfully" dilated and who, during the following 2 days, had remained totally symptomless and without changes in standard ECG were selected. Arrhythmias occurred in 18 patients: 12 had supraventricular arrhythmia, including 3 prolonged attacks of tachyarrhythmia due to atrial fibrillation; 6 had ventricular arrhythmia, with numerous extrasystoles in 5 cases and bursts of ventricular tachycardia in 1 case. Changes in ventricular repolarization were recorded as: (1) isolated T-wave modification (11 patients), and (2) ST-segment depression (11 patients) reaching or exceeding 2 mn in 5 cases and lasting from 4 to 33 minutes. These silent and transient electrical abnormalities were observed mostly during the 12 hours which followed transluminal angioplasty, and particularly after dilatation of the right coronary artery. The physiopathological mechanisms of these changes are uncertain, but their occurrence has no influence on mid-term results, i.e. the follow-up coronary arteriography at 6 months.

Although the Starr valve still is the most commonly used prosthesis, no systematic Doppler evaluation of its normal functioning has yet been performed. For this reason, 49 patients with mitral (25) or aortic (25) Starr valve and without evidence of cardiac failure, other valve disease or coronary disease were prospectively explored. Parameters measured were: maximum velocity, maximum and mean gradients, half-decrease time under pressure and corresponding valve areas. A. Mitral prosthesis. With Starr valves size 3 M and 4 M, corresponding to diameters of 30 and 32 mm respectively, the results obtained were: Vmax 1,7 +/- 0.3 m/s, maximum gradient 12.3 +/- 4.5 mmHg, mean gradient 5.3 +/- 2.2 mmHg, T1/2 120 + 30 ms, valve area 1.96 + 0.45 cm2. These 5 parameters were not significantly different with 3M and 4M valves. B. Aortic prosthesis. Contrary to mitral valve prosthesis, the results here were influenced by the size of the valve. With Starr valve No 10 (diameter 24 mm), values were: Vmax 3.3 +/- 0.4 m/s, maximum gradient 45 +/- 11.6 mmHg, mean gradient 26.7 +/- 8.8 mmHg. Aortic regurgitation was present in 20 p. 100 of the cases. The validity of the continuity equation was tested for non-invasive determination of the aortic valve functional area.

This study concerns 51 cases of mitral valve prolapse demonstrated on bidimensional 4 cavities sonography according to Gilbert's criteria and aims to determine the frequency of the associated valvular involvement, anatomically with sonography and functionally with the Doppler test. Sonography demonstrates a tricuspid valve prolapse in 79 p. cent of the cases and an aortic valve prolapse in 10 p. cent. The Doppler test demonstrates a tricuspid leakage in 52 p. cent of the cases, a pulmonary leakage in 62 p. cent, and an aortic leakage in 18 p. cent. The myxoid degeneration found in 60 p. cent of the cases is a major factor in the occurrence of complications, especially progressive cardiac insufficiency (A). The myxoid degeneration defines therefore the "isolated prolapse disease" as opposed to "the prolapse without myxoid degeneration" which is a pure sonographic entity and probably a variation of the normal (A). This cardiac insufficiency occurs late during the 6th or 7th decade and is due to mechanical factors: prolapse, chords rupture and annular dilatation.