Capecitabine-induced cardiotoxicity: case report and review of the literature.

Capecitabine, an oral prodrug of 5-fluorouracil (5FU), has been integrated into the management of multiple cancer types because of convenience of administration and efficacy comparable with 5fu. Cardiotoxicity induced by 5FU-in particular angina-has been well described in the literature, but reports of adverse cardiac events with capecitabine are also emerging. The mechanism underlying 5FU cardiotoxicity has long been thought to result from coronary vasospasm, but animal-model studies and patient echocardiographic findings both suggest a cardiomyopathic picture. Although 5FU cardiotoxicity is often reversible and can be managed supportively, presentations that are more severe-including arrhythmias, acute ischemic events, and cardiogenic shock-have been documented. In this report, we describe the case of a patient who ultimately required a pacemaker after developing symptomatic bradycardia and sinus arrest while receiving capecitabine for colon cancer.

Severe tricuspid regurgitation after heart transplantation.

BACKGROUND: Tricuspid regurgitation (TR) is common after heart transplantation. However, the incidence of severe TR and the incidence of symptoms after echocardiographic diagnosis of severe TR have not been documented. The purpose of this study is to determine the incidence of severe TR and its clinical significance in the heart transplant population. METHODS: We reviewed echocardiograms (echo) of all heart transplant patients coming for regular echocardiographic follow-up between 1990 and 1995. We reviewed the charts of all patients who had echo diagnosis of severe TR. RESULTS: A total of 336 patients had echo follow-up during this time period. The number of months post-heart transplant to last echo was 54 +/- 50 (range, 1 to 265 months). Ninety patients had moderate TR and 23 patients had severe TR. Mean time from heart transplantation to diagnosis of severe TR was 43 +/- 38 months (range, 1 to 132). Using Cutler-Ederer analysis, at 5 years, 92.2% of surviving patients were free from severe TR. At 10 years, 85.8% of surviving patients were free from severe TR. Of the 23 patients with severe TR, 17 had charts available for review. The mean number of prior endomyocardial biopsies was 28 +/- 21 (range, 3 to 88). These patients were followed for 35 +/- 18 months after diagnosis. During this period, they developed significant heart failure and peripheral edema. Six patients eventually underwent tricuspid valve replacement. CONCLUSIONS: Moderate to severe TR commonly occurs following heart transplantation. Severe TR is associated with significant morbidity.

Contrast echocardiography is superior to tissue harmonics for assessment of left ventricular function in mechanically ventilated patients.

BACKGROUND: Assessment of left ventricular function by echocardiography is frequently challenging in mechanically ventilated patients. We evaluated the potential value of contrast-enhanced imaging and tissue harmonic imaging over standard fundamental imaging for endocardial border detection (EBD) in these patients. METHODS AND RESULTS: Fifty patients underwent standard transthoracic 2D echocardiography and were imaged in fundamental and tissue harmonic modes and subsequently with intravenous contrast (Optison). Two echocardiographers reviewed all studies for ease of visualization of endocardial border segments and scoring of wall motion. EBD for each wall segment was graded from 1 to 4 (1 = excellent EBD). Wall motion was scored by a standard 16-segment model and 1 to 5 scale. Studies were categorized as nondiagnostic if 4 of 6 segments in the apical 4-chamber view were either poorly seen or not seen (EBD score 3 or 4). Quantification of ejection fraction was independently performed offline. Visualization of 68% of all segments improved with contrast echocardiography versus 17% improvement with tissue harmonics compared with fundamental mode. Significant improvement (poor/not seen to good/excellent) occurred in 60% of segments with contrast echocardiography versus 18% with tissue harmonics. A total of 850 segments were deemed poor/not seen, 78% of which improved to good/excellent with contrast echocardiography versus 23% with tissue harmonics. Interobserver agreement on EBD was 64% to 70%. Conversion of nondiagnostic to diagnostic studies occurred in 85% of patients with contrast echocardiography versus 15% of patients with tissue harmonics. Scoring of wall motion with fundamental mode, tissue harmonics, and contrast echocardiography was possible in 61%, 74%, and 95% of individual segments, respectively (P <.001). Wall motion scoring was altered in 17% of segments with contrast echocardiography and in 8% with tissue harmonics. Interobserver agreement on wall motion scoring was 84% to 88%. Contrast echocardiography permitted measurement of ejection fraction 45% (P =.003) more often over fundamental mode versus a 27% (P =.09) increase with tissue harmonics. CONCLUSIONS: Contrast echocardiography is superior to tissue harmonic imaging for EBD, wall motion scoring, and quantification of ejection fraction in mechanically ventilated patients.

Clinical outcome in the Marfan syndrome with ascending aortic dilatation followed annually by echocardiography.

This study reviewed the utility of echocardiography in following patients with the Marfan syndrome for whom cardiovascular complications, especially aortic root dilatation, dissection and rupture, are the major causes of morbidity and mortality. We conclude that echocardiography can be used to follow asymptomatic patients with the Marfan syndrome.

Native tissue harmonic imaging improves endocardial border definition and visualization of cardiac structures.

BACKGROUND: The purpose of this study was to examine the impact of native tissue harmonic imaging on endocardial border definition, wall motion scoring, and visualization of intracardiac structures. METHODS AND RESULTS: For wall motion analysis, 60 consecutive patients underwent standard transthoracic echocardiograms in both harmonic and fundamental modes. Three experienced echocardiographers reviewed each echocardiogram. Endocardial border definition for each wall segment was graded from 1 to 4 (1 = excellent endocardial definition). Wall motion was scored by using a standard 16-segment model and 1 to 5 scale. For visualization of cardiac structures, 50 consecutive patients were studied. Two experienced interpreters reviewed each echocardiogram for both normal and abnormal structures by using the following scoring scale: (1) harmonic is much better than fundamental, (2) harmonic is slightly better than fundamental, (3) harmonic and fundamental are equivalent, (4) fundamental is slightly better than harmonic, and (5) fundamental is much better than harmonic. Visualization of 64% (95% confidence interval [CI] 0.61 to 0.66) of all segments improved in harmonic mode, with 26% (95% CI 0.24 to 0.29) improving from poor/not seen to good/excellent. Of 444 segments deemed poor/not seen, visualization of 312 (70%) (95% CI 0.66 to 0.75) improved to good/excellent with harmonic mode. Of these 312 segments, 55% comprised the lateral and anterior walls on apical views. Interobserver agreement on endocardial border definition was 82% to 86%. Scoring of wall motion was altered in 171 of 1075 (16%) of segments by harmonic mode. This was significantly greater than the interobserver disagreement, which was only 10% (p<0.002). Mitral valve chordae and papillary muscles were visualized slightly/much better with harmonic mode in 40 of 50 echocardiograms. Left atrial boundaries were seen slightly/much better in harmonic mode in 29 of 50 studies. Abnormal structures were seen slightly/much better in harmonic mode in 12 of 14 cases. CONCLUSIONS: Native tissue harmonic imaging has significant impact on endocardial border definition and wall motion scoring and improves the visualization of both normal and abnormal cardiac structures.

T cell subsets in the thymus of graft-versus-host immunosuppressed mice. Sensitivity of the L3T4+Lyt-2- subset to cortisone.

We have investigated the effects of graft-versus-host disease on T cell differentiation in the murine thymus. We previously reported that GVH-induced thymic dysplasia results in a T cell immunodeficiency associated with a lack of IL-2 production. This deficiency in IL-2 production may be the result of a reduction in the number of L3T4+Lyt-2- IL-2-producing cells or of a functional defect in this population. To test these two alternatives, flow cytometry analysis of L3T4 and Lyt-2 antigen expression on thymocytes along with immunofluorescence microscopy were employed to assess T cell phenotypes in thymuses of GVH mice. GVH reactions were induced by injecting 40 x 10(6) C57BL/6 (B6) or A strain lymphoid cells into C57BL/6xAF1 (B6AF1) mice. Thymocyte populations were quantitated on different days after GVH induction. In the normal thymus, the ratio of L3T4/Lyt-2 single positive cells was greater than 2:1. In contrast, such a ratio was less than 1:1 in the atrophic GVH thymus, owing to a selective reduction in the number of L3T4+Lyt-2- cells. Following cortisone treatment the ratio of L3T4/Lyt-2 single positive thymocytes in normal F1 mice was approximately 3:1, whereas in GVH animals this ratio was reversed (1:2). This reversal was due to a selective reduction in the absolute numbers of L3T4+Lyt-2- cells. In adrenalectomized GVH animals, thymic cortical atrophy was prevented and normal ratios of L3T4/Lyt-2 single positive cells were observed. However, when these animals were treated with cortisone, the L3+T4/Lyt-2- population was more sensitive than was the L3T4- Lyt2+ population, thereby resulting in a 1:2 L3T4/Lyt-2 ratio. These results demonstrate that single positive L3T4 cells are present in the murine GVH thymus, yet they have not acquired cortisone resistance, a trait normally attributed to this mature thymic subset. It appears that the GVH dysplastic thymus can support the differentiation of L3T4+Lyt-2- cells--however, such a thymus is unable to confer cortisone resistance upon this population. Consequently, these cells appear to be eliminated when exposed to corticosteroids in peripheral lymphoid tissue.

The effects of polyinosinic:polycytidylic acid on the graft-versus-host reaction. III: Increased severity of the reaction with delayed pI:C treatment.

We have been investigating the effects of polyinosinic:polycytidylic acid (pI:C), an interferon inducer, on the graft-versus-host reaction. We have previously shown that pI:C treatment of C57BL/6xAF1 (B6AF1) recipient mice immediately before injection of C57BL/6 (B6) parental lymphocytes inhibited the immuno-suppression and pathological changes normally caused by the GVH reaction, by a mechanism apparently identical to that seen in F1 hybrid resistance (HR) to hematopoietic grafts. We now demonstrate that delaying pI:C treatment by as little as 48 hr produces the opposite effect. Treatment of recipient B6AF1 mice at different days after transfer of parental lymphocytes induced a marked increase in the severity of the GVH reaction, as measured by a decreased plaque-forming cell response to sheep erythrocytes; decreased proliferative response to the T and B cell mitogens PHA, Con A, and LPS; increased pathological changes in both lymphoid and nonlymphoid tissues; and increased GVH-associated mortality. This effect is unrelated to HR, as pI:C was able to augment the severity of the GVH reaction when A strain cells were injected into AxCBAF1 recipients, which do not manifest HR. Early pI:C treatment (1 and 2 days after parental cell transfer) increased the severity of the GVH reaction much more than later pI:C treatment (7 and 8 days after parental cell transfer). This observation, along with the demonstration of altered pathology in GVH mice treated with pI:C, suggests that the effect of pI:C is not mediated through a direct suppressive effect of IF on the cells responding in either the PFC or mitogen assays, but rather by the ability of IF to activate or suppress mechanisms involved in the development of GVH-induced alterations.