In monogenic disorders, correlation between genotype and phenotype is a premise for predicting prognosis in affected patients. Predictive genetic testing may enable prophylaxis and promote clinical follow-up. Although Marfan syndrome (MFS) is known as a monogenic disorder, according to the present diagnostic criteria a mutation in the gene FBN1 is not sufficient for the diagnosis, which also depends on the presence of a number of clinical, radiological, and other findings. The fact that MFS patient cohorts only infrequently have been examined for all relevant phenotypic manifestations may have contributed to inconsistent reports of genotype-phenotype correlations. In the Norwegian Study of Marfan syndrome, all participants were examined for all findings contained in the Ghent nosology by the same investigators. Mutation identification was carried out by robot-assisted direct sequencing of the entire FBN1 coding sequence and MLPA analysis. A total of 46 mutations were identified in 44 unrelated patients, all fulfilling Ghent criteria. Although no statistically significant correlation could be obtained, the data indicate associations between missense or splice site mutations and ocular manifestations. While mutations in TGF-domains were associated with the fulfillment of few major criteria, severe affection was indicated in two cases with C-terminal mutations. Intrafamilial phenotypic variation among carriers of the same mutation, suggesting the influence of epigenetic facors, complicates genetic counseling. The usefulness of predictive genetic testing in FBN1 mutations requires further investigation.

The prevalence of each single feature in the Ghent criteria in patients with Marfan syndrome (MFS) is not known. To elucidate this, a cross-sectional study of 105 adults with presumed MFS was carried out. All patients were examined by the same group of investigators with standardized and complete assessment of all features in the Ghent criteria. Eighty-seven (83%) fulfilled the criteria in 56 different variants. The most prevalent major criterion in Ghent-positive persons was dural ectasia (91%), followed by major genetic criterion (89%) and ectopic lenses (62 %). In 14 persons (16%), the diagnosis was dependent on the dural findings. In all, 79% fulfilled both major dural and major genetic (positive family history and/or FBN1 mutation) criteria, suggesting that most patients with MFS might be identified by investigating these criteria. A history or finding of ascending aortic disease was present in 46 patients (53%). This low prevalence might partly reflect a high number of diagnosed patients encompassing the whole spectrum of the syndrome. The study confirms the need to examine for the complete set of features in the Ghent criteria to identify all patients with MFS. The majority of persons with MFS might be identified by the combined assessment of dura mater and family history, supplemented with DNA analysis in familynegative cases. The low prevalence of ascending aortic disease might indicate better future prospects in an adult population than those traditionally considered.

The importance of nitric oxide (NO) in coronary blood flow (CBF) regulation was examined in anesthetized pigs. NO synthesis was inhibited by intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine (L-NNA). L-NMMA (30 mumol/min) reduced CBF (Doppler flowmetry) by 16.3% (13.1-20.2%; P < 0.001) and L-NNA (30 mumol/min) by 16.1% (13.9-18.9%; P < 0.001). During NO blockade, myocardial oxygen consumption was unaltered as an increase in oxygen extraction occurred due to a reduced partial pressure of oxygen and oxygen saturation in blood from the anterior interventricular vein. L-Arginine completely reestablished CBF after giving L-NMMA, but not after giving L-NNA. L-NNA reduced the coronary flow response to ADP by 66-83%, whereas the selected dose of L-NMMA did not affect it. The flow response to adenosine was not affected by either L-NMMA or L-NNA. L-NNA reduced reactive hyperemia after occluding the left anterior descending coronary artery for 10 and 30 s but not for 120 s. Our data show that NO produced in the coronary endothelium plays an important role in CBF regulation in vivo, accounting for approximately 16% of CBF and a major part of the flow response to ADP. NO also contributes to reactive hyperemia after brief, but not longer, ischemic periods.

Postoperative daily administration of 4 g of omega-3 fatty acids in heart transplant recipients is effective as hypertension prophylaxis, depending on increases in serum eicosapentaenoic and docosahexaenoic acids. Preservation of microvascular endothelial function, demonstrated by a more pronounced response to forearm skin ischemia in the treatment group, may contribute to the hypotensive role of omega-3 fatty acids.

Endothelin is released from the heart for several minutes during reperfusion following a brief coronary artery occlusion.

A female patient born in 1950 underwent plasma exchange and concomitant drug therapy for 20 yr due to homozygous familial hypercholesterolemia. Plasma exchange reduced total cholesterol levels from 25-30 mmol/L (967-1160 mg/dL) before treatment to 9.5 mmol/L (363 mg/dL) with regression of xanthomas and no side effects of long-term treatment. Due to end-stage calcific left ventricular outflow tract obstruction not amenable to standard valve reconstructive surgery, a combined heart-liver transplantation was successfully performed in 1996. She is without symptoms and living a normal life 4 yr after transplantation. Total cholesterol value is normal (4.7 mmol/L [182 mg/dL]) using a moderate dose of statins. Selective coronary angiography is without signs of graft vascular disease and the liver function is normal.

Summary:Lefi ventricular (LV) function and plasma levels of cardiovascular hormones were examined in patients with severe chronic congestive heart failure (CHF), randomized to placebo or enalapril, in addition to conventional therapy. M-mode echocardiography and plasma hormone concentrations were available at baseline and after 6 weeks of treatment. There was a significant relationship between LV systolic function and levels of angiotensin-Il and norepinephrine. Enalapril incmsed LV fractioiial shortening(FS%)( 13.3+-5.6to lSA&S.S,p

AVR with concomitant CABG in octogenarians with aortic stenosis who are otherwise healthy, may be performed without increased risk.