Neutral endopeptidase is activated in cardiomyocytes in human aortic valve stenosis and heart failure.

BACKGROUND: The regulation of the cardiac neutral endopeptidase (EC 24.10, NEP) that degrades bradykinin and natriuretic peptides has been investigated in human cardiac hypertrophy and heart failure. Methods and Results- NEP mRNA was quantitated by real-time polymerase chain reaction (PCR) in left ventricular biopsies from patients with aortic valve stenosis (AS, n=19) and heart failure due to dilated cardiomyopathy (DCM, n=14), and control subjects with normal systolic function (CON, n=14). Left ventricular NEP mRNA content was increased 3-fold in AS (P<0.005) and 4.1-fold in DCM (P<0.002). The increase in NEP mRNA was related to the increase in end diastolic pressure in AS and DCM. In a second series, myocardial NEP enzymatic activity was determined. It increased 3.6-fold in AS (P<0.02) and 4-fold in DCM (P<0.002). NEP was localized in the myocardium by immunofluorescence microscopy and in situ PCR to myocytes and nonmyocyte areas and cells. CONCLUSIONS: Elevated cardiac NEP activity in pressure loaded and failing human hearts may increase the local degradation of bradykinin and natriuretic peptides.

Upregulation of myocardial estrogen receptors in human aortic stenosis.

BACKGROUND: Estrogen receptor (ER)-mediated effects have been associated with the modulation of myocardial hypertrophy in animal models and in humans, but ER expression in the human heart and its relation to hypertrophy-mediated gene expression have not yet been analyzed. We therefore investigated sex- and disease-dependent alterations of myocardial ER expression in human aortic stenosis together with the expression of hypertrophy-related genes. METHODS AND RESULTS: ER-alpha and -beta, calcineurin A-beta, and brain natriuretic peptide (BNP) mRNA were quantified by real-time polymerase chain reaction in left ventricular biopsies from patients with aortic valve stenosis (n=14) and control hearts with normal systolic function (n=17). ER protein was quantified by immunoblotting and visualized by immunofluorescence confocal microscopy. ER-alpha mRNA and protein were increased 2.6-fold (P=0.003) and 1.7-fold (P=0.026), respectively, in patients with aortic valve stenosis. Left ventricular ER-beta mRNA was increased 2.6-fold in patients with aortic valve stenosis (P<0.0001). ER-alpha and -beta were found in the cytoplasm and nuclei of human hearts. A strong inverse correlation exists between ER-beta and calcineurin A-beta mRNA in patients with aortic valve stenosis (r=-0.83, P=0.002) but not between ER-alpha or -beta and BNP mRNA. CONCLUSIONS: ER-alpha and -beta in the human heart are upregulated by myocardial pressure load.

Impact of cardiac surgery using cardiopulmonary bypass on course of chronic lymphatic leukemia: a case-control study.

BACKGROUND: Chronic lymphatic leukemia (CLL) is a common disease among elderly individuals. The number of older patients undergoing operations with cardiopulmonary bypass (CPB) is increasing. The aim of the present study was to evaluate the impact of cardiac surgery using CPB on the long-term course of CLL. METHODS: From 1992 to 2000, a total of 28 patients with CLL underwent heart surgery using CPB at our institution (group I). These patients were compared with 25 patients from the CLL register who were retrospectively matched with regard to preoperative administration of chemotherapy, Binet classification, age, and sex (group II). A time-point was selected for each patient in group II so that the variables for the two groups corresponded in relation to the time of operation of the patients in group I. Midterm follow-up data in both groups were analyzed. RESULTS: There were no differences between groups regarding matched variables. The mean follow-up time was similar in both groups (2.6 +/- 2.2 vs 2.3 +/- 1.3 years, p > 0.5). The 30-day mortality in group I was 14.3%. The mean stay in the intensive care unit was 4.2 +/- 7.5 days; the median number of units of packed red blood cells transfused was three (range 0 to 17). Compared with group II, in group I significantly fewer patients (11 vs 17, p = 0.049) required chemotherapy significantly later (1.98 +/- 2.06 vs 0.84 +/- 1.18 years, p = 0.018). During follow-up, no difference was found between groups regarding severe infections (10 vs 14, p = 0.14). Despite postoperative mortality in group I, the long-term mortality was similar in both groups (p = 0.3). CONCLUSIONS: Cardiac surgery using CPB did not have a negative impact on the natural course of CLL. Moreover, this procedure seems to be associated with a decrease in the number of postoperative chemotherapy administrations and with an increase of chemotherapy-free survival time. Although CLL may be a risk factor in the early postoperative period, it is not a contraindication for cardiac surgery using CPB.

Huge pulmonary arteriovenous fistula: diagnosis and treatment and an unusual complication of embolization.

We report the case of a 42-year-old woman with Rendu-Osler-Weber syndrome (hereditary hemorrhagic telangiectasia) and a huge pulmonary arteriovenous fistula that involved the entire right middle lobe. She had a history of dyspnea and intermittent atrial flutter for 6 months. A chest radiograph showed a discrete shadowing of the middle part of the right lung. Arteriovenous fistula was suspected based on the echocardiographic finding of immediate bubble detection in the left atrium on introducing echocardiographic contrast medium into the venous system. Atrial shunt was excluded. Angiography revealed a huge pulmonary arteriovenous fistula in the entire middle lobe of the right lung. A trial of interventional embolization was performed, but the size of the fistula made it impossible to achieve complete closure of all segmental fistulas. Furthermore, the patient complained of unusual, severe chest pain after implantation of the first coil, so that the coil had to be removed. Therefore the patient underwent surgical resection of the entire right middle lobe and the upper part of the right lower lobe. Anatomy was clearly delineated and all connecting vessels were suture-closed, but both lungs showed diffuse microscopic superficial pulmonary arteriovenous fistulas, which were too small to be detected by angiography and which were also partly closed. The postoperative course was uneventful: the patient recovered completely, she no longer had shortness of breath, and blood gas analysis showed normal P(aO)(2). It is not clear whether the patient's improved physical performance will last, because the development of diffuse microscopic arteriovenous fistulas bilaterally in the lungs is not predictable. Therefore close follow-up is necessary and in the case of recurrence (ie, enlargement of the existing small fistulas), early interventional embolization should be performed.