[A young woman with fulminant pulmonary embolism]. / Fulminante Lungenembolie bei einer jungen Frau.

We describe the case of a 24-year-old woman who was admitted to the emergency department with dyspnea and sinus tachycardia. The suspected diagnosis of pulmonary embolism was confirmed by computed tomography (CT) scan. The patient lost consciousness soon afterwards and was found to be pulseless. Cardiopulmonary resuscitation was performed and high dosis thrombolysis was given. The patient survived without sequelae and was discharged on oral anticoagulation from the hospital 8 days after the initial admission. In our opinion unknown factor-V Leiden in combination with a local form of hormonal contraception (NuvaRing®) was responsible for the deep venous thrombosis of the left leg and the pulmonary embolism.

Diagnostic and prognostic value of serial dobutamine stress echocardiography for noninvasive assessment of cardiac allograft vasculopathy: a comparison with coronary angiography and intravascular ultrasound.

BACKGROUND: Routine methods for surveillance of cardiac allograft vasculopathy (CAV) are coronary angiography and intravascular ultrasound (IVUS). This study analyzed the diagnostic and prognostic value of dobutamine stress echocardiography (DSE) for noninvasive assessment of CAV. METHODS AND RESULTS: In 109 heart transplant recipients, 333 DSEs were compared with 285 coronary angiograms and 199 IVUS analyses. Studies were repeated after 1, 2, 3, 4, and >/=5 years in 88, 74, 37, 18, and 7 patients, respectively. Resting 2D echocardiography detected CAV defined by IVUS and angiography with a sensitivity of 57% (specificity 88%). DSE increased the sensitivity to 72% (P=0.002). M-mode analysis increased the sensitivity of 2D rest and stress analysis (P=0.001, 0.004). Cardiac events occurred after 1.9% of normal stress tests by 2D analysis (combined 2D and M-mode: 0%), compared with 6.3% (3.8%) of normal resting studies. Worsening of serial DSE indicated an increased risk of events compared with no deterioration (relative risk 7.26, P=0.0014). Serial deterioration detected by stress only was associated with a higher risk of events than changes evident from resting studies (relative risk 3.06, P=0.0374). CONCLUSIONS: DSE identifies patients at risk for events and facilitates monitoring of CAV. A normal DSE predicts an uneventful clinical course and justifies postponement of invasive studies. The prognostic value of DSE is comparable to that of IVUS and angiography.

Rapid cardiovascular action of aldosterone in man.

Rapid nongenomic in vitro effects of aldosterone have been demonstrated recently in cultured vascular smooth muscle and endothelial cells. But there is, as yet, little evidence for corresponding in vivo effects. The present study thus investigates the rapid nongenomic effects of aldosterone on human cardiovascular function. In a double-blind placebo-controlled randomized parallel trial on 17 patients with suspected coronary heart disease, the effect of 1 mg aldosterone iv on cardiovascular function was assessed during cardiac catheterization. Hemodynamic parameters (such as heart rate, left ventricular and atrial pressures, arterial pressures, vascular resistances, and cardiac output) were measured before and 3 and 10 min after administration of aldosterone or placebo. Significant changes were found for systemic vascular resistance, cardiac output, and cardiac index, compared with the placebo group (Wilcoxon test, P < 0.02-0.05). The effect of aldosterone dissipated within 10 min. The results are in line with the in vitro data cited above and consistent with earlier findings on acute cardiovascular effects of aldosterone, which have now been confirmed and extended by contemporary techniques. The hypotheses of rapid nongenomic in vivo effects of aldosterone are further substantiated by this study.

Predictors of reduced coronary flow reserve in heart transplant recipients without angiographically significant coronary artery disease.

BACKGROUND: Determination of coronary flow reserve (CFR) is increasingly used to assess the functional significance of cardiac allograft vasculopathy. Although the relation between CFR and angiographically defined vasculopathy has been studied extensively, little is known about other factors determining CFR in heart transplant recipients without significant lesions by coronary angiography. METHODS: Sixty consecutive patients were studied 0.5 to 148 months after heart transplantation with intracoronary Doppler and intravascular ultrasound. An endothelium-independent CFR< or =2.5 was defined as abnormal. Stepwise logistic regression analysis was used to identify factors (demographic data of donor and recipient, lipid profile, epicardial vessel morphology by intravascular ultrasound, left ventricular hypertrophy, acute rejection episodes, and hemodynamics) potentially associated with a reduced CFR. RESULTS: Only the presence of left ventricular hypertrophy (48% vs. 14%, P=0.007 and P=0.023, bivariate and multivariate analysis, respectively) and higher donor ages (41+/-12 vs. 29+/-11 years, P=0.002 and P=0.013, bivariate and multivariate analysis, respectively) showed an independent association with an abnormal flow reserve. CFR in patients with left ventricular hypertrophy was reduced due to higher baseline flow velocities (27+/-11 vs. 20+/-6 cm/sec, P=0.004). Furthermore, resting flow velocity increased as a function of donor age (r=0.264, P=0.047), while hyperemic flow velocity was not different. Other patient characteristics and hemodynamics did not affect CFR. CONCLUSION: The presence of left ventricular hypertrophy and higher donor ages independently contribute to a reduced CFR in patients after heart transplantation. This reduction in CFR is due to elevated baseline flow velocities rather than to a change in hyperemic flow velocities. These findings should be taken into account for the interpretation of reduced CFR values obtained by intracoronary Doppler in heart transplant recipients without angiographically overt coronary lesions.

Dobutamine stress echocardiography for noninvasive diagnosis of cardiac allograft vasculopathy: a comparison with angiography and intravascular ultrasound.

This study was performed to assess the value of dobutamine stress echocardiography for noninvasive diagnosis of cardiac allograft vasculopathy (CAV) compared with coronary angiography and intravascular ultrasound (IVUS) in 50 consecutive orthotopic heart transplant recipients. In 46 of 50 patients, a technically adequate echocardiogram could be obtained. Using a 16-segment model, a total of 675 segments were analyzed. At rest, wall motion abnormalities were found in 61 of 675 (9.0%) left ventricular segments in 15 of 46 patients. At maximal dobutamine stress, 103 of 675 segments (15.3%) had wall motion abnormalities (25 of 46 patients). Based on IVUS and angiographic findings, patients were allocated to 2 groups. Group I (n=18) had absent or only mild intimal hyperplasia (mean IVUS grade < or = 3.0 on a 6-grade scale). Group II (n=28) had moderate to severe intimal hyperplasia (mean grade > 3.0 with or without angiographic evidence of CAV. The prevalence of wall motion abnormalities was significantly higher in group II than in group I, both at rest (50 of 415 vs 11 of 270 coronary segments in 13 of 28 vs 2 of 18 patients) and during maximal stress (88 of 415 vs 15 of 270 coronary segments in 22 of 28 vs 3 of 18 patients). Quantitative M-mode echocardiography demonstrated decreased wall thickening in group II versus group I patients at maximal dobutamine dosage in the septum (48 +/- 18% vs 61 +/- 17%; p < 0.01) as well as in the left ventricular posterior wall (77 +/- 21% vs 96 +/- 21%; p <0.005). Regional myocardial dysfunction as assessed by dobutamine stress echocardiography was associated with IVUS evidence of moderate to severe intimal hyperplasia. Dobutamine stress echocardiography appears to be a feasible noninvasive method for detection of CAV in heart transplant recipients, which may reduce the need for routine coronary angiography.

Cyclosporine versus tacrolimus (FK 506) for prevention of cardiac allograft vasculopathy.

This study prospectively compared the impact of cyclosporine A and tacrolimus on the development of cardiac allograft vasculopathy. By using serial intravascular ultrasound examinations, a trend toward a more pronounced progression was noted in the tacrolimus group in the first year after heart transplantation.

Adult human cardiomyocytes coexpress vimentin and Ki67 in heart transplant rejection and in dilated cardiomyopathy.

BACKGROUND: The aim of this study was to investigate whether adult human cardiomyocytes may reexpress vimentin and whether this is linked to cellular activation. METHODS: Myocardial samples of 81 heart transplant recipients (n=183) and patients with dilated cardiomyopathy (n=10) were investigated by immunohistochemistry with the use of the marker molecule vimentin, the muscle-specific protein desmin, and Ki67, a marker for cell activation. RESULTS: Vimentin protein expression in cardiomyocytes was found in 28 samples of transplant recipients and 5 myocardial samples of patients with dilated cardiomyopathy. Coexpression of vimentin and Ki67 was found in 52 of 340 vimentin-positive cardiomyocytes. CONCLUSIONS: We suggest that the vimentin/Ki67 coexpression indicates cell activation processes as the result of different growth stimuli.

Functional and morphological findings in heart transplant recipients with a normal coronary angiogram: an analysis by dobutamine stress echocardiography, intracoronary Doppler and intravascular ultrasound.

BACKGROUND: Coronary angiography is still the routine screening method for cardiac allograft vasculopathy in most transplant centers. This study was designed to analyze functional and morphologic changes in heart transplant recipients with normal angiographic findings. METHODS: Dobutamine stress echocardiography and intracoronary ultrasound were obtained in 56 patients with a normal coronary angiogram 41+/-31 months after heart transplantation. Intracoronary Doppler flow velocity measurements before and after intracoronary adenosine administration were performed in 34 of 56 patients. Any regional wall motion abnormalities detected by stress echocardiography were regarded as abnormal. By quantitative intracoronary ultrasound analysis using a 6-grade scale, a mean grade of all coronary segments >3.0 was defined as significant intimal hyperplasia. RESULTS: Only 17 patients (30%) showed both a normal dobutamine stress echocardiogram and absence of significant intimal hyperplasia by intravascularultrasound. Abnormal findings were observed in 39 patients (70%): both by dobutamine stress echocardiography and intravascular ultrasound in 22 patients, by intravascular ultrasound alone in 11 patients, and by dobutamine stress echocardiography alone in 6 patients. Coronary flow velocity reserve did not discriminate between patients with normal or abnormal intravascular ultrasound or dobutamine stress echocardiographic findings. CONCLUSIONS: Only a minority of heart transplant patients with a normal coronary angiogram is free of pathological changes, when assessed by intravascular ultrasound and dobutamine stress echocardiography. Coronary flow velocity reserve does not seem useful to further characterize these patients.

Detection of humoral rejection in human cardiac allografts by assessing the capillary deposition of complement fragment C4d in endomyocardial biopsies.

BACKGROUND: There are no well-established diagnostic criteria to detect humoral rejection in organ transplantation. The value of commonly used markers in immunohistochemistry, such as C1q, C3c, IgG, IgM and fibrinogen, is questioned by some groups. Complement fragment C4d is a more stable marker of complement activation as it is covalently bound to graft capillaries. C4d has been shown to identify clinically relevant, but otherwise undetectable humoral anti-graft reactions in human kidney transplants. METHODS: Immunohistochemical techniques were used to evaluate 155 endomyocardial biopsies from 56 heart transplant recipients less than 3 months post transplantation for the presence of capillary C4d staining. In a subset of patients, C4d staining was compared with C1q, C3c, IgM and fibrin staining and was correlated with clinical outcome. RESULTS: Within 3 months 9 of 56 patients died. Five of these nonsurvivors had prominent C4d staining (p < .05), whereas C1q, C3c and IgM showed no correlation with clinical outcome. Presence of fibrin correlated with clinical outcome and C4d staining (p < .05). CONCLUSIONS: The capillary deposition of complement split product C4d in human endomyocardial biopsies was significantly associated with graft loss. Determination of fibrin deposition may yield additional information to establish a diagnosis of humoral rejection. The immunohistochemical assessment of capillary deposition of C4d and fibrin appears to be an appropriate tool for the identification of patients, who may require additional or alternative immunosuppressive therapy targeted against the humoral immune system.

Intravenous Albunex during transesophageal echocardiography: quantitative assessment by videodensitometry and integrated backscatter analysis from unprocessed radiofrequency signals.

This study investigates the comparative sensitivity of video and radiofrequency imaging to detect changes of the myocardial acoustic properties after intravenous Albunex. Thirty-six patients received Albunex, 0.08 and 0.22 ml/kg intravenously, during transesophageal imaging of the ventricular short axis. Analysis of video images was performed in all patients and of radiofrequency data in 20 patients. Although myocardial videointensity remained unchanged, 57% of the myocardial backscatter plots demonstrated significant contrast enhancement. The study demonstrates that intravenous Albunex is capable of myocardial contrast enhancement and proves the diagnostic superiority of radiofrequency compared with video imaging. Ultrasonic radiofrequency imaging may provide a technical basis for future noninvasive assessment of myocardial perfusion.

Transpulmonary contrast echocardiography: effects on delineation of endocardial border, assessment of wall motion and interobserver variability in stress echocardiograms of limited image quality.

BACKGROUND: A major limitation of stress echocardiography remains poor image quality. OBJECTIVE: To investigate the effects of transpulmonary contrast echocardiography (TCE) with BY 963 on endocardial border delineation, detectability of wall motion abnormalities and interobserver variability at rest and during dobutamine stress echocardiography (DSE) in subjects with technically limited baseline echocardiograms. METHODS: BY 963 was administered intravenously to 36 patients (5 ml for parasternal LAX/SAX, 10 ml for apical four-chamber/two-chamber view) both at rest and at peak stress during DSE. Two observers applied a delineation score (0, endocardial border not visible; 1 border poorly visible; and 2, border clearly visible) to 12 wall segments in the parasternal and 10 in the apical views both before and after administration of BY 963. A 16-segment wall-motion score was used. RESULTS: In parasternal views, the delineation score was not improved by TCE. In the apical views, TCE significantly increased the delineation score (from 14.1 +/- 5.4 to 20.7 +/- 4.2 at rest and from 14.6 +/- 5.7 to 21.7 +/- 4.1 under stress, both P< 0.01). For 18 of 25 patients with coronary artery disease (> or = 70% stenosis) results of DSE were positive before TCE, whereas results were positive for 21 patients during TCE. For 10 of 11 patients without coronary artery disease, results of DSE were negative both before and during TCE. For the apical delineation score, interobserver variability was decreased significantly by TCE (from 19.5 +/- 19.6 to 8.2 +/- 15.6% at rest and from 20.2 +/- 19.6 to 3.3 +/- 11.4% at peak stress, both P< 0.01). CONCLUSIONS: TCE enhances endocardial border delineation in apical views at rest and during DSE, resulting in a decrease of interobserver variability and an improvement in assessment of wall motion. Use of TCE, at least how it was applied in this investigation, seems not to be indicated for parasternal projections.

Clinical pharmacokinetics after a single oral dose of oxilofrine.

In a combined pharmacokinetic and clinical trial the correlation was investigated between plasma levels of oxilofrine and the haemodynamic effects on eight healthy volunteers after an oral dose of 120 mg oxilofrine. Plasma levels of free oxilofrine were measured by capillary gas chromatography mass fragmentography. Cardiovascular as well as echocardiographic parameters (left ventrical extent and velocity of fractional shortening) have been measured. The results pharmacokinetically showed a marked enterohepatic reabsorption profile with a second oxilofrine plasma peak occurring in between the second and third hours. The heart rate and mean arterial blood pressure remained unchanged. The total peripheral resistance was deceased on average. Systolic blood pressure increased by a maximum of 13.8%, the diastolic decreased by 8.8%. Increasing of the extent of left ventrical fractional shortening by 20.9% and the velocity by 29.5% indicated a positive inotropic effect, which was long lasting and not accompanied by chronotropic effects. There is a direct positive correlation between oxilofrine plasma levels and the extent of fractional shortening of left ventrical diameter (r = 0.981).