William E. Hopkins

Frequency and significance of intrapulmonary right-to-left shunting in end-stage hepatic disease

Intrapulmonary vascular abnormalities consisting of arteriovenous malformations and capillary dilatations have been described in patients with severe liver disease. These intrapulmonary vascular abnormalities can result in intrapulmonary right-to-left shunting and hypoxemia. Twenty-five of 53 patients (47%) with end-stage hepatic disease were found to have contrast echocardiographic evidence of intrapulmonary right-to-left shunting. There was no difference in mean age, gender distribution, or severity of hepatic disease in those with and without evidence of such shunting. Although there was no difference in mean partial arterial oxygen pressure (PaO2) values in the 2 groups (82 +/- 11 vs 76 +/- 11 mm Hg), the mean PaO2 value of those with at least 2+ left ventricular opacification (2 to 4+) was significantly lower (66 +/- 3 mm Hg, n = 8; p less than 0.01). Unexpectedly, patients with evidence of intrapulmonary shunting had a lower mortality rate before transplantation (3 of 25, 12%) than those without evidence of shunting (10 of 28, 36%) resulting in a significant difference in actuarial survival (p less than 0.05) by the end of the follow-up period. It is concluded that intrapulmonary right-to-left shunting occurs frequently in patients with end-stage liver disease and may be a marker of a positive biologic process that, in some way, leads to improved short-term survival.

Right ventricular dysfunction in low output syndrome after cardiac operations: Assessment by transesophageal echocardiography

BACKGROUNDnLow output syndrome after cardiac operations is associated with high morbidity and mortality rates. The contribution of right ventricular dysfunction to this syndrome has not been fully characterized. The purpose of this study was to evaluate the utility of transesophageal echocardiography to identify the frequency and the in-hospital mortality from right ventricular dysfunction in patients with this syndrome.nnnMETHODSnSeventy-five consecutive patients undergoing transesophageal echocardiography for low output syndrome early after cardiac operations were evaluated. The findings from transesophageal echocardiography were correlated with the type of surgical procedure, cross-clamp time, right heart hemodynamics, and coronary angiography.nnnRESULTSnRight ventricular systolic dysfunction occurred in 36 patients (42%); in 17 patients it was isolated and in 19 patients it occurred in combination with left ventricular dysfunction. Postoperative right ventricular dysfunction was not uniformly associated with important right coronary artery disease or with prolonged ischemic time during cardiopulmonary bypass. Hemodynamic data were not useful to distinguish the group with postoperative right ventricular dysfunction. Patients with right ventricular dysfunction had a high (44%) in-hospital mortality rate.nnnCONCLUSIONSnRight ventricular dysfunction occurs frequently in patients with low output syndrome after cardiac operations and is associated with a high in-hospital mortality rate. Better understanding of the mechanisms causing postoperative right ventricular dysfunction may provide insight for preventing this complication.

Intravenous albunex during dobutamine stress echocardiography: Enhanced localization of left ventricular endocardial borders

Albunex is an intravenous contrast agent that opacifies the left ventricle (LV). This study evaluated the effect of Albunex on the enhancement of LV endocardial border localization during dobutamine stress echocardiography (DSE). Albunex was infused in 30 patients at baseline and with low- and high-dosage dobutamine. Apical two- and four-chamber views were divided into six segments each, and enhancement of LV border localization was compared with precontrast images graded as follows: 0 = none; 1 = faint; or 2 = optimal. The mean grade and percentage of segments with optimal localization of LV endocardial borders were determined. There was a significant increase in enhancement with low- and high-dosage dobutamine when compared with baseline. Of 179 segments with suboptimal enhancement at baseline, 137 (77%) became optimal during DSE with Albunex. We conclude that Albunex improves localization of LV endocardial borders and that this localization is enhanced during DSE.

Mechanisms contributing to increased synthesis of plasminogen activator inhibitor type 1 in endothelial cells by constituents of platelets and their implications for thrombolysis.

We recently hypothesized that after pharmacologically induced coronary thrombolysis, increased activity of plasminogen activator inhibitor type 1 (PAI-1) retards recanalization, contributes to early reocclusion, or both. This hypothesis was based on the increased elaboration of PAI-1 that we observed in cultured liver cells exposed to growth factors releasable from platelets activated at sites of thrombosis in vivo. PAI-1 released locally is particularly likely to attenuate lysis of thrombi that are targets of thrombolytic drugs. Accordingly, the present study was performed to determine whether synthesis of PAI-1 by endothelial cells is augmented by products of platelets. Lysates from platelets (0.5-8.0 x 10(4)/mm3 media, i.e. less than 10% of the concentration of platelets in blood) increased synthesis and release of PAI-1 into both the extracellular matrix and conditioned media (by 2.8-fold and 3.3-fold within 6 and 24 hours, respectively). Synthesis of neither tissue-type plasminogen activator nor overall protein increased. Increased synthesis of PAI-1 was confirmed by immunoprecipitation of [35S]PAI-1 after metabolic labeling of cells. The increased elaboration of PAI-1 was consistent with increased transcription as reflected by the observed increase in PAI-1 mRNA of 2.2-fold in 4 hours. Effects of platelet lysates were simulated by transforming growth factor beta (TGF-beta), known to be present in platelet alpha-granules and released with platelet activation. Antibody to TGF-beta reduced the stimulation of PAI-1 synthesis by TGF-beta, as expected, by 82%.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential attenuation of fibrinolysis by growth factors released from platelets and their pharmacologic implications

Increased concentrations of the fast-acting tissue-type plasminogen activator (t-PA) inhibitor attenuate the fibrinolytic activity of pharmacologically administered activators of the fibrinolytic system such as t-PA. Accordingly, it was hypothesized that augmentation of synthesis and elaboration of inhibitor from the liver, leading to increased concentrations of inhibitor in plasma, or from endothelial cells in the vicinity of thrombi undergoing lysis, leading to increased concentrations locally, may contribute to failure of pharmacologically induced thrombolysis or to early reocclusion. Because platelets are rich in transforming growth factor beta and epidermal growth factor-like activity, it was thought that release of growth factors from platelets activated in vivo could mediate increases of the inhibitor in plasma by stimulating its formation in the liver and its local release from endothelial cells in the vicinity of thrombi. If so, fibrinolysis might be rendered more effective by concomitant prevention of platelet growth factor release. Transforming growth factor beta, a major constituent of platelets, increased concentrations of the t-PA inhibitor messenger ribonucleic acid (mRNA) in human hepatoma cells in a specific and dose-dependent manner. A peak effect was seen with 5 ng/ml and a 10-fold increase in 6 hours. Release of inhibitor protein into conditioned media increased as well. Induction of the inhibitor mRNA increase was elicited by exposure as brief as 30 minutes. Cycloheximide, an inhibitor of protein synthesis, was not inhibitory. The mechanisms responsible differed from those seen with epidermal growth factor, shown previously in the laboratory to increase inhibitor mRNA. In addition, the 2 factors were synergistic. Platelet lysates elicited effects simulating those of the purified growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesophageal echocardiography in the detection of cardiovascular sources of peripheral vascular embolism

The purpose of this study was to determine the impact of transesophageal echocardiography (TEE) on the management of patients with peripheral vascular emboli. We prospectively evaluated the role of TEE in 15 patients with documented peripheral emboli and no evidence of occlusive peripheral vascular disease. The patients were divided in two groups for analysis: group 1 (n=8) had no clinical evidence of heart disease and group 2 (n=7) had clinically significant heart disease. TEE provided information regarding the source of embolism in four (50%) patients in group 1, and these findings significantly affected the management of all. Three patients underwent thoracic surgery to remove the source of embolism (aortic valve mass in one and a thrombus in the descending thoracic aorta in two); the other patient was treated with thrombolytic agents. TEE findings had high diagnostic value in all patients in group 2, but the results had a possible effect on clinical management in only two of these patients. TEE provides diagnostic information in most patients with peripheral vascular emboli and this information has a significant influence on management, particularly in those without clinically evident heart disease. TEE should be performed in all patients with documented peripheral embolism.

Right and left Ventricular Area and Function Determined by Two-Dimensional Echocardiography in Adults with the Eisenmenger Syndrome from a Variety of Congenital Anomalies

The Eisenmenger syndrome has been associated with right ventricular (RV) enlargement and systolic dysfunction. However, little attention has been directed toward potentially characteristic changes in left ventricular (LV) dimensions or function. Therefore, 2-dimensional echocardiography (short-axis-papillary muscle level) was performed in 24 adults (mean age 33 +/- 7 years) with Eisenmenger syndrome to evaluate RV and LV size and function. A significant correlation was found between RV and LV end-diastolic areas (r = 0.96; regression slope 1.06), and fractional area change (r = 0.88; regression slope 1.03) in patients with a nonrestrictive ventricular septal defect (VSD) (n = 15). In contrast, in patients with Eisenmenger syndrome but no VSD (n = 9), RV and LV end-diastolic areas (r = 0.68; regression slope 0.10), and fractional area change (r = 0.08; regression slope -0.09) were discordant. RV function was preserved in most patients with a VSD, and mean RV fractional area change was significantly greater than in those without a VSD (0.50 +/- 0.13 vs 0.18 +/- 0.08; p < 0.001). No significant difference was apparent in these 2 groups (patients with and without a VSD) with respect to age, pulmonary artery systolic pressure, partial arterial oxygen pressure or hematocrit. Thus, the results indicate a relation between biventricular chamber dimensions and systolic function that is dependent on the nature and locus of the primary intracardiac defect responsible for the Eisenmenger syndrome.

Angiotensin-converting enzyme inhibitors in adults with cyanotic congenital heart disease

Abstract In carefully selected patients with cyanotic congenital heart defects, the response to systemic afterload reduction with ACE inhibitors appears favorable. A more comprehensive controlled trial to assess the hemodynamic and functional effects of ACE inhibitors in such patients should be undertaken.

Quantitative Ultrasonic Tissue Characterization of Myocardium in Cyanotic Adults with an Unrepaired Congenital Heart Defect

Adults with nonrestrictive ventricular septal defects have chronic hypoxemia that may lead to alterations in myocardial structure and function. Ultrasonic integrated backscatter provides quantitative assessment of myocardial acoustic properties that are altered by myocardial ischemia, fibrosis, and edema. Sixteen patients (age 31 +/- 10 years) with a nonrestrictive ventricular septal defect were studied using 2-dimensional and M-mode echocardiography with integrated backscatter imaging to determine the cyclic variation of integrated backscatter in the right ventricular free wall, ventricular septum, and left ventricular posterior wall. Cyclic variation of integrated backscatter in the right ventricular free wall and interventricular septum in patients was significantly less than that in control subjects (4.1 +/- 0.8 vs 4.9 +/- 1.0 decibels [dB], p = 0.02, and 3.8 +/- 1.2 vs 4.8 +/- 1.1 dB, p = 0.004, respectively). There was no difference between mean cyclic variation of integrated backscatter in the left ventricular posterior wall in patients and that in control subjects (4.7 +/- 1.3 vs 4.8 +/- 1.1 dB, p = NS, respectively). However, values < 4.0 dB were noted in 38% of patients compared with 15% of control subjects. Biventricular systolic function was normal in all but 1 patient. There was no correlation between backscatter and either wall thickness or percent wall thickening from the 3 regions. Histologic analysis of myocardial tissue in 3 patients revealed interstitial and replacement fibrosis. Adults with nonrestrictive ventricular septal defects exhibit alterations in tissue-acoustic properties detectable by integrated backscatter imaging despite preserved systolic function and wall thickening.

Usefulness of dobutamine stress echocardiography for the prospective identification of the physiologic significance of coronary narrowings of moderate severity in patients undergoing evaluation for percutaneous transluminal coronary angioplasty.

Dobutamine stress echocardiography (DSE) was performed after coronary angiography to evaluate the need to perform percutaneous transluminal coronary angioplasty (PTCA) for 46 stenoses of moderate severity (50% to 80%) in 46 patients. Patients were divided into 2 groups according to the DSE results in the distribution of the coronary artery with the lesion of moderate severity: group I (n = 32) were those without inducible myocardial ischemia; PTCA was not performed. Group II (n = 14) were those who exhibited myocardial ischemia; PTCA was performed in 12. The 2 groups were comparable in terms of clinical characteristics. Follow-up DSE was performed < or = 48 hours after PTCA, at 3 months, and 6 to 12 months after the first DSE. In group I at 3 months, DSE results were still negative in the distribution of the vessel with the moderately severe lesion in 24 patients; only 1 patient had a positive result, and 8 patients who refused DSE remained clinically stable. At 6 to 12 months (mean 7 +/- 2), 26 patients had negative study results; 3 patients who refused follow-up DSE remained clinically stable. In group II, 12 of 14 patients with inducible ischemia on the initial DSE underwent PTCA. Early follow-up DSE (< or = 48 hours) was negative in 7, and 4 had persistent inducible wall motion abnormalities in the myocardium subtended by the coronary artery in which the PTCA had been performed; 1 study was not performed.(ABSTRACT TRUNCATED AT 250 WORDS)