Safety and efficacy of a new transpulmonary echo contrast agent in echocardiographic studies in patients.

OBJECTIVES: This study was designed to investigate in patients the effect of a new transpulmonary echo contrast agent, made from 5% human serum albumin (Albunex), on systemic and pulmonary hemodynamics and the influence of the contrast doses on left ventricular opacification. BACKGROUND: New intravenous transpulmonary echo contrast agents are promising, allowing contrast stress echocardiography and myocardial contrast echocardiography. Nevertheless, some shortcomings still remain. Thus, the pulmonary hypertension observed in pigs after Albunex injection should be investigated in humans, and the optimal dose of contrast agent remains to be determined because previous experiments indicated that the left ventricular opacification and attenuation are dose dependent. METHODS: Albunex in doses of 0.08 and 0.22 ml/kg was successively injected intravenously in 20 catheterized patients; in 11 of them, anti-inflammatory drugs were withdrawn to avoid the blocking of an eventual thromboxane-mediated pulmonary artery hypertension. Systemic blood pressure and pulmonary artery, capillary wedge and right atrial pressures were continuously monitored. Cardiac output, left ventricular fractional shortening and blood gases were determined 5 min before and 5 and 10 min after each injection. The left ventricular opacification was qualitatively assessed by three independent observers using a grading scale from 0 to 3, with 0 indicating an absence of contrast effect and 3 indicating full opacification. RESULTS: No clinical, hemodynamic or respiratory adverse reactions were observed in any patient. Irrespective of doses, a left ventricular opacification grade > or = 2 was observed in 74% of the 35 injections that could be evaluated. This percentage increased to 94% when the higher dose group was considered alone. CONCLUSIONS: This first report of the effect of Albunex injected intravenously on pulmonary artery pressures in humans demonstrates that this contrast agent appears to be safe. The significant left ventricular opacification obtained in a majority of patients without an important increase in attenuation supports the use of the higher dose of the contrast agent.

Enhanced natriuretic response to neutral endopeptidase inhibition in heart-transplant recipients.

Heart-transplant recipients (Htx) generally present with body fluid and sodium handling abnormalities and hypertension. To investigate whether neutral endopeptidase inhibition (NEP-I) increases endogenous atrial natriuretic peptide (ANP) and enhances natriuresis and diuresis after heart transplantation, ecadotril was given orally to 8 control subjects and 8 matched Htx, and levels of volume-regulating hormones and renal water, electrolyte, and cyclic guanosine monophosphate (cGMP) excretions were monitored for 210 minutes. Baseline plasma ANP, brain natriuretic peptide (BNP), and cGMP were elevated in Htx, but renin and aldosterone, like urinary parameters, did not differ between groups. NEP-I increased plasma ANP (Htx, 20.6+/-2.3 to 33.2+/-5.9 pmol/L, P<0.01; controls, 7.7+/-1. 2 to 10.6+/-2.6 pmol/L) and cGMP, but not BNP. Renin decreased similarly in both groups, whereas aldosterone decreased significantly only in Htx. Enhanced urinary sodium (1650+/-370% versus 450+/-150%, P=0.01), cGMP, and water excretions were observed in Htx and urinary cGMP positively correlated with natriuresis in 6 of the Htx subjects. Consistent with a normal circadian rhythm of blood pressure, without excluding a possible effect of NEP-I, mean systemic blood pressure increased similarly in both groups at the end of the study (6.9+/-2.0% versus 7.4+/-2.8% in controls and Htx). Thus, systemic hypertension, mild renal impairment, and raised plasma ANP levels are possible contributory factors in the enhanced natriuresis and diuresis with NEP-I in Htx. These results support a physiological role for the cardiac hormone after heart transplantation and suggest that long-term studies may be useful to determine the potential of NEP-I in the treatment of sodium retention and water retention after heart transplantation.

Anatomic, clinical, and therapeutic features of acute cardiac rupture. Successful surgical management fourteen hours after myocardial infarction.

A 62-year-old man sustained an acute myocardial infarction complicated on the thirteen hour by left ventricular rupture and acute periocardial tamponade. Echocardiography confirmed the suspicion of intrapericardial fluid, and immediate pericardiocentesis improved the hemodynamic state for a period sufficient to permit preparation for operation. Resection of ruptured and necrotic anteroapical left ventricular myocardium with primary reconstruction was successfully accomplished with the aid of temporary extracorporeal circulation. The patient has remained well for 1 year after the operation. Anatomic, clinical, and therapeutic features of acute cardiac rupture are discussed.

Endothelin participates in increased circulating atrial natriuretic peptide early after human heart transplantation.

BACKGROUND: Hemodynamic improvement after heart transplantation is expected to normalize the neuroendocrine balance, but circulating atrial natriuretic peptide (ANP) remains elevated. Endothelin stimulates ANP secretion and its concentration increases after heart transplantation, suggesting a role for this peptide in the cardiovascular adaptative response to heart transplantation. METHODS: To investigate whether endothelin may induce ANP increase in heart transplant recipients, we monitored daily ANP, endothelin, and related hormonal, biologic, and hemodynamic parameters before and during the first week after either heart transplantation (n = 15) or coronary artery bypass grafting (n = 10). RESULTS: Surgery induced a transient secretory peak of arginine vasopressin and endothelin in both groups at day 1. Bypass grafting did not modify normal ANP (11.8 +/- 2.1 pmol/L), endothelin (2.4 +/- 0.3 pmol/L), renin activity (0.11 +/- 0.04 pmol/L/sec), or aldosterone (492 +/- 122 pmol/L) values. Heart transplantation normalized the renin-aldosterone axis, but the early decrease observed for ANP (from 27.2 +/- 4.8 to 21.14 +/- 1.4 pmol/L) was only partial and transient. Endothelin further increased (from 4.4 +/- 0.8 to 9.14 +/- 1.8 pmol/L; p < 0.01) after transplantation. Positive correlations were observed between endothelin, isoproterenol dose, creatinine, right atrial pressure, and ANP, but multiple correlation analysis showed the important role of endothelin (r = 0.69, p < 0.001). Cyclic guanosine monophosphate correlated with ANP (r = 0.65, p < 0.001). CONCLUSIONS: Elevated endothelin, suggesting vascular dysfunction, likely contributes to the ANP increase observed early after heart transplantation. Furthermore, ANP, through a cardiac endothelium feedback, may act in the maintenance of circulatory homeostasis in heart transplant recipients.

Normal short-term renal response to acute volume expansion in heart transplant recipients: a role for atrial natriuretic peptide?

BACKGROUND: The breakdown of blood pressure and body fluid homeostasis observed in heart transplant (Htx) recipients may partly be due, as in heart failure, to a blunted renal response to elevated atrial natriuretic peptide (ANP). METHOD: This possibility was addressed through determination of the relationship between ANP, the urinary cyclic guanosine monophosphate (cGMP), a biologic marker of ANP renal activity, and the early renal responses to 10 mL/kg isotonic saline infusion over 30 minutes in 8 control subjects and 8 matched Htx recipients. RESULTS: Urine flow, natriuresis, and urinary cGMP excretion increased similarly in both groups, resulting in elimination of, respectively, 1/2 and 2/3 of the sodium and the water load during the experiment that lasted 4 hours and 30 minutes. Plasma renin and aldosterone decreases were similar in both groups. Elevated ANP further increased in Htx after saline infusion (from 19.5 +/- 3.7 to 33.8 +/- 5.6 pmol/L, P < .001). Plasma cGMP paralleled ANP in both groups (r = 0.81; P < .001). Significant correlations were observed between plasma ANP and urinary cGMP excretion (r = 0.48, P < .025 and r = 0.43, P < .05 in Htx recipients and control subjects) and between plasma ANP and urinary sodium excretion (r = 0.64, P < .001 in Htx recipients). CONCLUSION: In spite of a relative renal hyporesponsiveness to the cardiac hormone, with higher plasma ANP being not associated with increased renal excretions in Htx recipients, ANP is likely to participate in the appropriate short-term renal response to acute volume expansion in Htx recipients.

A malignant primary cardiac pheochromocytoma.

We report the case of a malignant primary cardiac pheochromocytoma treated by adjuvant cytotoxic chemotherapy after surgical resection, with a 5-year survival. There is no specific chemotherapy for malignant pheochromocytoma, but because it has the same embryologic origin as neuroblastoma, we used similar chemotherapy. Because of unexpected malignancy potential, we think that total and meticulous resection of the tumor must be done.

Transaortic approach in double-outlet right ventricle with subaortic ventricular septal defect.

The standard approach (right ventriculotomy and atriotomy) for surgical repair of double-outlet right ventricle with subaortic ventricular septal defect and pulmonary stenosis may not give an adequate view of the intracardiac defect due-to the presence of anomalous coronary artery anatomy or unusual cavity spacial relationship. Thus, a transverse aortotomy was performed and the left ventricular outflow tract was well visualized through the aortic valve and could be reconstructed precisely. Therefore, the transaortic approach also should be considered for systemic route reconstruction in this group.

Intrapericardial teratoma in a newborn infant: use of fetal echocardiography.

The case of an infant with intrapericardial benign teratoma, which was suspected in utero after fetal echocardiography, is reported. This new approach permitted very early diagnosis and surgical treatment before cardipulmonary distress appeared. The tumor was excised completely, and the patient was asymptomatic three months postoperatively.

Vascular and neuroendocrine components in altered blood pressure regulation after surgical repair of coarctation of the aorta.

STUDY OBJECTIVE: To investigate potential vascular and neuroendocrine determinants of altered blood pressure (BP) regulation in patients previously operated on for aortic coarctation. DESIGN, SETTING AND PATIENTS: We prospectively re-evaluated 45 patients operated on for aortic coarctation at Strasbourg University Hospital over a 13-year period. Four of these patients were less than 2 years old at the time of the operation and four were older than 20 years. Patient age and time since the operation were on average 21+/-13 years and 8+/-3 years, respectively. Surgery consisted of a resection with end-to-end anastomosis for 18 patients, angioplasty (8), prosthesis (4) or sub-clavian flap (15). RESULTS: Despite repair of the coarctation, about 40% of the patients showed an abnormal BP status at rest. The majority of these patients had uncomplicated borderline hypertension. The orthostasis test as well as the BP circadian rhythm were frequently abnormal. While the ankle/arm systolic pressure index measured at rest was generally within the normal range, diminished carotid-femoral pulse wave velocity was observed. Plasma adrenaline and aldosterone levels were elevated in about 50% of the patients examined. CONCLUSIONS: These new findings suggest that there are 'cause and effect' relationships between aortic structural and functional vascular abnormalities, and augmented plasma adrenaline and aldosterone in some patients after coarctation repair. These phenomena are likely to be involved in altered BP regulation and might result in recurrent hypertension.

Contrast echocardiography in coronary artery diseased patients: effect of systemic and pulmonary artery pressures on left heart opacification after intravenous injection of Albunex.

BACKGROUND: Contrast echocardiography is a useful tool for assessing repeatedly patients with coronary artery disease. Nevertheless, elevated pulmonary artery and systemic blood pressures likely to be associated with cardiac ischemia may limit the left ventricular opacification (LVO) because of the microspheres' sensitivity to pressure. OBJECTIVE: To determine the effects of systemic and pulmonary artery blood pressures on LVO. METHODS: We performed 55 intravenous injections (0.08 and 0.22 ml/kg) of a new transpulmonary contrast agent (Albunex), during two separated exposures, into 20 cardiac ischemic patients while monitoring invasively their cardiac indexes, and intracardiac, systemic, and pulmonary artery blood pressures. LVO was graded qualitatively from faint to full. RESULTS: A logistic model with the grade of LVO as the dependent variable and a selection from among the dose, exposure, right and left atrial blood pressures, systolic systemic and pulmonary artery blood pressures (ranges 94-208 and 14-45 mmHg, respectively), cardiac index, stroke index, and pulmonary and systemic vascular resistances as the explanatory variables demonstrated that increasing the dose gives an increasing probability of LVO (P = 0.02) and that increasing the pulmonary artery pressure reduces that probability (P = 0.006). A decreased cardiac index tended also to be associated with decreased LVO. The systemic blood pressure and the pulmonary and systemic vascular resistances had no statistically significant effect on the grade of LVO. CONCLUSIONS: LVO after intravenous administration of Albunex is dose-dependent and limited by an elevated pulmonary artery pressure. These data suggest that one should use higher doses for cardiac ischemic patients with elevated pulmonary artery pressures and that use of Albunex has the potential to detect pulmonary hypertension in patients.

Is a prosthetic ring required for mitral repair of mitral insufficiency due to posterior leaflet prolapse? Long-term results in 96 patients submitted to repair with no ring.

OBJECTIVE: It is a common statement that every mitral repair should be stabilized by some type of prosthetic mitral ring. In the very specific situation of isolated prolapse of the posterior leaflet (PPL), this statement may be enhanced by the possible anatomically discontinuity of the mitral annulus. This article concerns 96 patients with 'isolated' PPL (IPPL) who were operated upon without ring insertion. Long-term follow-up was obtained in order to ascertain the survival, stability of the repair and the need for reoperation, thus justifying or not the lack of use of a ring. METHODS: A total of 96 patients, 70 male and 26 female, underwent mitral repair for mitral insufficiency (MI) almost exclusively caused by PPL. Age ranged from 33 to 81 years (mean 60.7+/-11.3). All underwent quadrangular resection of the prolapsed portion and plication of the annulus. In 69 cases local stabilization was achieved by four U stitches, two on each side of the plication, passed through and sutured on some flexible material, 2-3 cm in length. Twenty seven patients had no such local reinforcement. RESULTS: There was one case of early death (1%) caused by refractory hypoxemia in a patient with long lasting pre-operative pulmonary edema. Two patients were lost for follow-up after 2 months. Follow-up was from 0.2 to 14.7 years (mean 4.5), for a total of 422.7 patient-years. There were four late deaths at a mean of 6-year follow-up (0.9-10 years). Actuarial survival was 95.5 and 90.5% at 5 and 8 years, respectively. Event-free for recurrence of significant mitral insufficiency (MI) was 96 and 92% at 5 and 8 years. Event-free of thromboembolic or hemorrhagic events was 84.3 and 72.3% at 5 and 8 years. Event-free from reoperation was 97.8 and 94% at 5 and 8 years. CONCLUSION: One can conclude that (a) IPPL repair without insertion of a ring is safe and long-lasting (b) the incidence of late death, recurrence of MI, thromboembolic/hemorrhagic events, need for reoperation, is not higher in this subset of patients than in conventional repair (c) such repair might work better and for a longer time, as reaction and sclerosis resulting from ring insertion are avoided (d) minor advantages could be due to an easier surgical procedure, especially through a minimally invasive approach.

Cardiac myxoma with glandular component: case report and review of the literature.

A 7 cm diameter tumor of the left atrium is reported in a 78 year-old woman with a past history of pT3N1M0 colonic adenocarcinoma. The histological examination of the atrial tumor disclosed areas of highly vascularized myxoid stroma with cells strongly reactive for vimentin. Multiple mucoid spaces lined by a single layer of goblet cells were scattered among those typical areas of myxoma. No nuclear atypia was observed. Cytoplasm of the glandular cells was immunoreactive for epithelial antisera (keratin, EMA), CEA and CA19.9. Two years later, the patient was doing well, with no local recurrence of the cardiac myxoma and no secondary location of the colonic adenocarcinoma. The histological characteristics, the absence of atypia, the absence of tumoral extension or neoplastic lymphatic vascular thrombi in the pedicle or in the interatrial septum, and the finding of typical myxomatous areas supported the diagnosis of cardiac myxoma with glandular component. To our knowledge, 21 cases of myxoma with glandular mucinous component, focal or prominent, have been previously published in the literature. These myxoma were generally sporadic cases with the same clinical features and prognosis as typical myxoma. Immunoreactivity of these glandular structures was constant for epithelial markers. The positive immunostaining by CEA, and by CA19.9 in our case, reflects the histogenetic endodermal origin.

Safety of a new transpulmonary echocontrast agent (Albunex) in repeated echocardiographic studies in patients.

BACKGROUND AND HYPOTHESIS: Multiple contrast-enhanced echocardiographic studies are to be expected in patients with cardiac ischemic disease, but the sonication process used to produce the echocontrast agent Albunex may result in new epitopes that could cause an immunogenic response. METHODS: Repeated exposures to intravenous Albunex over a period of time long enough to allow development of an eventual immune reaction were performed in 12 patients while monitoring for lymphocyte transformation, microsphere specific IgE and IgG antibodies, and systemic, pulmonary artery, capillary wedge, and right atrial pressures, as well as cardiac output, left ventricular fractional shortening, and blood gases. RESULTS: No significant 3H-thymidine incorporation and thus no specific blastic transformation of the patients' lymphocytes were observed either for high or low Albunex concentrations, corresponding to the expected hepatic and plasma concentrations of microspheres. No formation of microsphere-specific IgE and IgG antibodies was observed after the first or second Albunex exposure. Furthermore, no clinically significant hemodynamic or respiratory adverse reactions were observed in any patient. CONCLUSION: These results suggest that repeated exposures to intravenous Albunex induce no adverse effect on the cellular and humoral immune systems and on left and right heart hemodynamics in patients.

Treatment of a distal splenic artery aneurysm with splenic conservation. A case report.

We report the case of a successful treatment of a splenic artery aneurysm by aneurysm excision and direct splenic artery reconstruction allowing spleen conservation. This aneurysm was related to an arterial wall medianecrosis. Because of the reappraisal of the splenic immunological function, we believe as others that this surgical management can be a new alternative to splenectomy as treatment of splenic artery aneurysms.

Arterial emboli of the upper extremity: a persisting problem.

From 1969 to 1980, 154 emboli of the upper extremities (UEE) were managed in our institution. They occurred in 151 patients, 66 males (44%) and 85 females (56%) aged ranged from 23 to 87 years (mean 68.9). Obstruction level was in the subclavian artery (12 cases), the axillary artery (46), the brachial artery (74 cases), the radial or ulnar artery (22 cases). Cardiac disease was present in 119 cases. Ischemia was severe in 47 cases (30%), and partial in 104 (67%). Peripheral gangrene was already present in 2 cases. 106 patients were operated on within 10 hours after the occurrence of UEE (69%). Associated systemic emboli was noted in 10 cases. The treatment consisted in 140 primary embolectomies and in 11 cases of conservative therapy (heparin 10, thrombolysis 1). Reoperation was done in 11 patients (7%) because of recurrence of UEE and in 4 cases (2%) for post-operative thrombosis. Results were good in 128 patients with clinical improvement and arterial patency.

Acute post-infarction left ventricle rupture. Five operations with three long-term survivals.

Cardiac rupture is cause of death in myocardial infarction. Surprisingly only seventeen successful attempts at operative treatment have been published, with a rather good long term survival. The authors report five cases of cardiac rupture operated upon with two deaths and three long term survivals. Frequency, clinical features and surgical possibilities are discussed with particular insistance on a rather aggressive surgical attitude when considering this complication.

Albumin as a sealant for a polyester vascular prosthesis: its impact on the healing sequence in humans.

OBJECTIVE: Although the healing characteristics of albumin impregnated vascular prostheses have been extensively studied in animal models, they have never been studied in humans. We therefore examined the healing sequence and the albumin degradation rate of this type of prosthesis harvested from humans. We also addressed the possible relationship between the implantation of cross-linked albumin and a specific inflammatory reaction. METHODS: Thirty albumin-impregnated polyester vascular prostheses were collected in our institution from January 1991 to February 1993. The mean duration of implantation of the prostheses was 8.4+/-9.7 (SD) months (range: 1 hour to 26 months). Twenty two prostheses were patent at the time of explantation and 4 had been thrombosed for less than 24 hours. In 18 cases, the prostheses were surgically removed because of a complication or a reoperation, and during an autopsy in 12 cases. Each harvested specimen was submitted to histological and immunohistochemical studies in order to demonstrate the presence of human albumin sealant, and to determine the inflammatory cell constituents. RESULTS: The albumin-impregnated prostheses were poorly infiltrated by healing tissues after 2 years of implantation. An external capsule was constantly observed after 2 months of implantation with a nonspecific chronic inflammatory reaction localized between the capsule and the polyester yarns. We observed large amounts of albumin sealant after 2 months, a gradual degradation with time, and traces after 2 years of implantation in humans. The luminal surface of the explant was mainly covered with organized fibrin. No histological signs of a specific inflammatory reaction were observed. CONCLUSIONS: The healing of the albumin impregnated prosthesis was poor and the degradation rate of the albumin sealant was significantly delayed, when compared to animal models. This difference in degradation rate could be related to interspecies differences of phagocytic cells enzymatic machinery. Finally, implantation of glutaraldehyde cross-linked albumin in humans is safe, since we observed an aspecific chronic foreign body inflammatory reaction.

[Right juxtaposition of the atria. Apropos of one case without associated trunco-conal abnormalities]. / Juxtaposition droite des auricules. A propos d'une observation sans anomalie tronco-conale associée

A child of 7 had coarctation of the aorta and an atrial septal defect. In the course of surgery to close the septal defect, she was found to have a right-sided juxtaposition of the appendages. This is a very rare abnormality, with no symptoms of its own, but usually associated with severe cardiac malformations especially of the truncus and conus. This case report is most unusual because of the right-sided disposition of the appendages and the absence of any serious associated cardiac lesion.

[Diastolic coronary prolapse in partial left pericardial agenesis]. / Effacement diastolique coronaire dans l'agénésie péricardique gauche partielle.

A few rare cases of coronary artery stenosis and occlusion have been reported in partial left pericardial agenesis. The authors report a privileged observation of partial left pericardial agenesis associated with an atrial septal defect in which diastolic collapse of the left marginal artery was demonstrated; this chronology was confirmed by synchronous analysis. The peroperative findings may explain the pathogenesis of the coronary disease encountered in this type of malformation, providing a new diagnostic sign of partial left pericardial agenesis.

[Surgical treatment of a single ventricle. Apropos of 4 operated cases]. / Traitement chirurgical du ventricule unique. A propos de 4 cas opérés

A surgical operation with a "curative" aim has been performed on four patients with a lone ventricle. It consisted of a IA type in 3 cases and IC type in one. There were one operative death and three long-term survivals. The operation consisted essentially in: a delicate step of partition of the lone cavity and the treatment of the often combined, and sometimes complex, heart malformation. The trauma to the conduction pathways is one of the major dangers of this type of operation and should be avoided or decreased by the detection during operation of the His bundle. Operation should be indicated in badly tolerated forms. Stenosis of the infundibulo-pulmonary pathway interferes with the development of a hypertensive pulmonary arteriolitis, seems to be a favourable element for surgical correction. In the absence of such stenosis, one should perform a banding early enough or discuss the indication for an intracardiac operation in relation with the pulmonary artery resistance.