Andreas Mügge

Echocardiography in infective endocarditis: reassessment of prognostic implications of vegetation size determined by the transthoracic and the transesophageal approach

In 105 patients with active infective endocarditis, disease-associated complications defined as severe heart failure (New York Heart Association class IV), embolic events and in-hospital death were correlated to the vegetation size determined by both transthoracic and transesophageal echocardiography. A detailed comparison between anatomic and echocardiographic findings, performed in a subgroup of 80 patients undergoing surgery or necropsy, revealed that true valvular vegetations can be reliably identified by echocardiography in the vast majority of patients; the detection rate was significantly higher for the transesophageal (90%) than for the transthoracic (58%) approach, particularly when infected prosthetic valves were evaluated. However, an accurate echocardiographic differentiation between true vegetations and other endocarditis-induced valve destruction (ruptured leaflets or chordae) is impossible. The correlation of vegetation size with endocarditis-associated complications showed that patients with a vegetation diameter greater than 10 mm had a significantly higher incidence of embolic events than did those with a vegetation diameter less than or equal to 10 mm (22 of 47 versus 11 of 58; p less than 0.01). Particularly for patients with mitral valve endocarditis, a vegetation diameter greater than 10 mm was highly sensitive in identifying patients at risk for embolic events. Vegetation size, however, was not significantly different in patients with and without severe heart failure or in patients surviving or dying during acute endocarditis. In addition, no significant correlation was found between vegetation size and location of endocarditis or type of infective organism.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective attenuation of endothelium-mediated vasodilation in atherosclerotic human coronary arteries.

This study was undertaken to determine whether atherosclerosis impairs relaxations mediated by endothelium-derived relaxing factor (EDRF) in human coronary arteries. Epicardial coronary arteries were obtained from the hearts of cardiac transplantation patients with or without histologically documented coronary atherosclerosis (atherosclerotic arteries were from patients aged 42–55 years, nonatherosclerotic arteries were from patients aged 14–24 years). Transverse strip preparations were mounted in organ baths for isometric tension recording. Tension was induced with prostaglandins F2a. Indomethacin (10−9 M) was present to prevent possible interference from endogenously formed prostaglandins. The EDRF-mediated relaxations in response to substance P (10−10 to 10−5 M), bradykinin (10−9 to 10−7 M), and Ca2+-Monophore A23187 (10−9 to 10−7 M) were significantly attenuated in atherosclerotic arteries. In deendothelialized tissues these compounds had no effect. In contrast, endothelium-independent relaxations induced by isoprenaline (10−7 to 10−5 M) were not affected by atherosclerosis. Atherosclerotic arteries showed also normal relaxations with high concentrations of glyceryl trinitrate (10−3 to 10−7 M), but reduced relaxations with a lower concentration of the compound (10−9 M). Acetylcholine (10−7 to 10−6 M) only produced endothelium-dependent relaxations in 8 of 60 arterial preparations (with or without atherosclerosis). In. most of the arteries, it was a direct vasoconstrictor (which may have masked EDRF release in many cases). Omission of indomethacin from the bath solution increased the incidence of moderate acetylcholine-induced relaxations (9 of 16 preparations). It is concluded that atherosclerosis attenuates EDRF-mediated vasodilation in epicardial human coronary arteries and that this impairment could promote coronary vasospasm and myocardial ischemia.

Diagnosis of noninfective cardiac mass lesions by two-dimensional echocardiography. Comparison of the transthoracic and transesophageal approaches.

This study was conducted in 46 patients with cardiac thrombi, 15 patients with atrial myxomas, and 32 patients with other cardiac or paracardiac tumors. Diagnoses were subsequently proven by surgery, autopsy, computed tomography, magnetic resonance imaging, or angiography in all patients. All patients underwent precordial and transesophageal two-dimensional echocardiography to assess the various mass detection rates. Atrial myxomas and predominantly left-sided cardiac tumors were identified by both echocardiographic techniques with comparable detection rates. Left ventricular apical thrombi were detected more frequently by precordial echocardiography. In contrast, transesophageal echocardiography was superior in visualizing left atrial appendage thrombi, small and flat thrombi in the left atrial cavity, thrombi and tumors in the superior vena cava, and masses attached to the right heart and the descending thoracic aorta. These data indicate that transesophageal echocardiography leads to a clinically relevant improvement of the diagnostic potential in patients in whom cardiac masses are suspected or have to be excluded in order to ensure the safety of clinical procedures.

Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: Identification of a subgroup of patients at increased embolic risk

OBJECTIVESnThis study was conducted to identify a subgroup of patients with nonrheumatic atrial fibrillation with an increased risk for cardiogenic embolism by assessing left atrial appendage function.nnnBACKGROUNDnPatients with nonrheumatic atrial fibrillation have an increased risk for thromboembolic complications. The left atrial appendage is the most likely source for thrombus formation. It is likely that the appendage function (contraction, filling dynamics) is related to the pathogenesis of thrombus formation.nnnMETHODSnTwenty-nine patients with nonrheumatic atrial fibrillation (group I) underwent biplane transesophageal echocardiography. The maximal and minimal areas during a cardiac cycle and the peak emptying and filling velocities of the appendage were measured in both scan planes. For comparison, two additional groups were also analyzed. Group II consisted of 12 patients with chronic atrial fibrillation due to significant mitral stenosis, and group III consisted of 30 patients who were in sinus rhythm.nnnRESULTSnPatients with nonrheumatic atrial fibrillation showed two distinct appendage flow patterns: either well defined peak filling and emptying waves (> or = 25 cm/s) with visible fibrillatory contractions of the appendage wall (high flow profile) or irregular, very low, peak filling and emptying waves (< 25 cm/s) associated with almost no visible appendage contractions (low flow profile). The left atrial appendage function in the first subgroup resembles that seen in patients with sinus rhythm, whereas the appendage function in the latter subgroup resembles more the static pouch seen in patients with rheumatic atrial fibrillation. Events suggestive of cardiogenic embolism occurred in six patients from group I, five of whom were in the low flow profile subgroup (p < 0.05). The spontaneous echo contrast phenomenon was observed in 80% of the low flow profile subgroup but in only 5% in the high flow profile subgroup (p < 0.05). Three thrombi confined to the left atrial appendage were detected by transesophageal echocardiography in group I; all three of the patients were in the low flow profile subgroup.nnnCONCLUSIONSnThe assessment of left atrial appendage function by transesophageal echocardiography may be helpful to identify subgroups of patients with nonrheumatic atrial fibrillation with an increased risk of thrombus formation.

Diagnosis of patent foramen ovale by transesophageal echocardiography and association with cerebral and peripheral embolic events

This study compares the value of transthoracic (TTE) and transesophageal (TEE) color Doppler and contrast echocardiography for detecting a patent foramen ovale (PFO). A total of 238 patients were studied: 74 patients with a history of otherwise unexplained ischemic stroke, transient cerebral ischemic attacks or peripheral embolic events (group A), 48 with a history of similar episodes explained by other cardiac abnormalities (group B), and 116 with no embolic events (group C). A PFO was detected by contrast TEE in 50 of 238 patients (21%) compared with 45 patients (19%) by color Doppler TTE. In a subgroup of 198 patients, TEE results could be compared with TTE findings. No patient had a PFO identified by color Doppler TTE. Contrast TTE detected a PFO in 15 patients (8%) compared with contrast TEE which demonstrated a PFO in 44 of 198 patients (22%) (p less than 0.001). Prevalence of PFO by TEE was 22, 21 and 22% in groups A, B and C, respectively. A PFO was present in 50% of patients aged less than 40 years and otherwise unexplained ischemic stroke; this percentage was higher (p less than 0.05) than corresponding values found in all other groups. Thus, contrast and color Doppler TEE are significantly superior to TTE for detecting PFO. The prevalence of PFO is significantly increased in young adults with otherwise unexplained ischemic stroke.

Supplementation of hypercholesterolaemic rabbits with L-arginine reduces the vascular release of superoxide anions and restores NO production

L-arginine, the precursor of endogenous nitric oxide (NO), has been shown to enhance endothelial function and to reduce intimal plaque area in cholesterol (Chol)-fed rabbits. We have studied endogenous NO production in such animals in vitro (endothelium-dependent relaxations) and in vivo (assessed by urinary NO3- excretion) before and during chronic oral administration of L-arginine and inhibitor of NO synthesis, L-NAME. Vascular superoxide anion (O2-) production of aortic rings was measured under basal conditions and following exposure to phorbol-myristate-acetate (PMA). Cholesterol feeding reduced endothelium-dependent relaxations and decreased urinary NO3- excretion. These effects were potentiated by administration of L-NAME. L-arginine partly restored endothelium-dependent relaxations and increased NO3- excretion. PMA-stimulated O2- production was increased in aortic rings from rabbits given cholesterol ( +159 +/- 28%; mean +/- S.E.M.) or cholesterol + L-NAME ( +149 +/- 37%) as compared with controls ( -22 +/- 7%). In rabbits given cholesterol + L-arginine, O2- production was decreased to control levels ( +14 +/- 17%; P < 0.05). We conclude that the systemic synthesis of NO is impaired in cholesterol-fed rabbits, as indicated by the decreased urinary excretion of NO3-. Enhanced O2- production may further contribute to the decreased biological activity of NO in hypercholesterolaemia. L-arginine restores endothelial function in hypercholesterolaemia by enhancing NO production and by protecting NO from early breakdown by O2-.

Identification of patent foramen ovale permitting paradoxic embolism

OBJECTIVESnWe sought to analyze the morphologic and functional characteristics of the patent foramen ovale in patients with different clinical likelihoods for paradoxic embolism.nnnBACKGROUNDnThe incidence of patent foramen ovale is increased in patients with otherwise unexplained arterial ischemic events. Because signs of venous thrombosis are absent in most patients, the diagnosis of paradoxic embolism is often questioned, even when patent foramen ovale is the only potential explanation for the ischemic event.nnnMETHODSnSeventy-eight patients with a patent foramen ovale detected by contrast transesophageal echocardiography were studied: 21 patients with an otherwise unexplained arterial ischemic event and clinical evidence implying paradoxic embolism (group I), 30 patients with an unexplained ischemic event but no clinical evidence for paradoxic embolism (group II) and 27 patients without an ischemic event (group III).nnnRESULTSnDuring transesophageal contrast echocardiography, patients in group I had more severe right to left shunting (mean +/- SD 52 +/- 16% of the left atrial area filled with contrast medium) and a wider opening of the patent foramen ovale (7.1 +/- 3.6-mm separation between the septum primum and the septum secundum) than did patients in group II (35 +/- 15% and 4.4 +/- 3.2 mm, respectively, p < 0.001) or group III (23 +/- 12% and 3.0 +/- 2.0 mm, respectively, p < 0.001). The incidence of atrial septal aneurysm was similar in the three groups. Severe contrast shunting (> or = 50% of the left atrial area filled with contrast medium) and wide opening of the patent foramen ovale (> or = 5-mm separation) revealed a high sensitivity (71% and 86%, respectively) and high specificity (86% and 96%, respectively) for identification of group I patients.nnnCONCLUSIONSnRight to left contrast shunting is more severe and opening of the patent foramen ovale is larger in patients with ischemic arterial events considered to be due to paradoxic embolism. In patients with a patent foramen ovale as the only potential cause for ischemic events and no signs of venous thrombosis, morphologic and functional variables assessed by transesophageal echocardiography may be helpful in estimating the likelihood of paradoxic embolism.

Dietary l-arginine and α-tocopherol reduce vascular oxidative stress and preserve endothelial function in hypercholesterolemic rabbits via different mechanisms

Vascular oxidative stress brought about by superoxide radicals and oxidized low-density lipoproteins (oxLDL) is a major factor contributing to decreased NO-dependent vasodilator function in hypercholesterolemia and atherosclerosis. We investigated whether chronic administration of L-arginine (2% in drinking water) or of alpha-tocopherol (300 mg/day) improves endothelium-dependent vasodilator function and systemic NO production, reduces vascular oxidative stress, and reduces the progression of atherosclerosis in cholesterol-fed rabbits with pre-existing hypercholesterolemia. Systemic NO production was assessed as urinary nitrate excretion; oxidative stress was measured by urinary 8-iso-PGF2alpha excretion in vivo, by lucigenin-enhanced chemiluminescence of isolated aortic rings ex vivo, and by copper-mediated LDL oxidation in vitro. Endothelium-dependent relaxation was almost completely abrogated in cholesterol-fed rabbits. Urinary nitrate excretion was reduced by 46+/-10%, and 8-iso-PGF2alpha excretion was increased by 61+/-18% as compared to controls (each P <0.05). Vascular superoxide radical release stimulated by PMA ex vivo was increased by 273+/-93% in this group, and the lag time of LDL oxidation was reduced by 35+/-6% (each P <0.05). Treatment with L-arginine and alpha-tocopherol reduced intimal lesion formation (by 68+/-6 and 4+/-11%, respectively; P <0.05) and improved endothelium-dependent relaxation. Both treatments also normalized urinary 8-iso-PGF2alpha excretion. L-Arginine increased urinary nitrate excretion by 43+/-13% (P <0.05) and reduced superoxide radical release by isolated aortic rings to control levels, which was unaffected by vitamin E treatment. By contrast, vitamin E dramatically increased the resistance of isolated LDL to copper-mediated oxidation in vitro by 178+/-7% (P <0.05), which was only marginally prolonged by L-arginine. Intimal thickening was reduced by both treatments. We conclude that both L-arginine and alpha-tocopherol reduce the progression of atherosclerotic plaques in cholesterol-fed rabbits. However, while L-arginine increases NO formation and reduces superoxide release, alpha-tocopherol antagonizes mainly oxLDL-related events in atherogenesis. Thus, both treatments reduce urinary isoprostane excretion and improve endothelium-dependent vasodilation via different mechanisms.

Response of human coronary arteries to aggregating platelets: importance of endothelium-derived relaxing factor and prostanoids.

Epicardial human coronary arteries (HCA) were obtained during heart transplantation. Strip preparations were mounted for isometric tension recording. Tension was induced with prostaglandin F2α (0.3–3 μM). Aggregating human platelets (107/ml and 108/ml) caused marked relaxation it the endothelium of the HCA was intact, but produced modest additional constriction if the endothelium was removed. The endothelium-dependent relaxations to platelets were slightly enhanced in the presence of methysergide (1 μM) or after treatment of the platelets with the thromboxane synthase inhibitor dazmegrel (1 mM, 30 minutes). Relaxations to platelets were markedly inhibited or abolished in the presence of apyrase (1 unit/ml), after selective pretreatment of HCA with gossypol or methylene blue (both 30 μM, 30 minutes), or after addition of hemoglobin (20 μM) to the organ bath. Pretreatment of HCA (not the platelets) with aspirin (30 μM, 30 minutes) had no significant effect on platelet-induced relaxations. Adenosine 5-diphosphate (0.1–100 μM) induced marked relaxations in endothelium-intact and much smaller relaxations in endothelium-denuded HCA. A low concentration (10 nM) of serotonin (5-HT) produced modest endothelium-dependent relaxations, higher concentrations (0.1–1 μM) led to increases in tension (also in the presence of endothelium). The thromboxane A2 mimetic U44069 (1–100 nM) was the most potent constrictor of HCA irrespective of the presence or absence of endothelium. After inhibition of thromboxane synthase, platelets produced large amounts of prostaglandins E2 and F2α. Both prostaglandins constricted HCA, which can explain the limited effects of dazmegrel. These data suggest that adenine nucleotides released by aggregating platelets stimulate the endothelial cell layer of HCA to produce endothelium-derived relaxing factor. The factor is able to override the direct vasoconstrictor effects of other platelet products (5-HT, thromboxane A2, and prostaglandin E2) and may be an important defense mechanism against coronary vasospasm.

Quantification of tricuspid regurgitation by Doppler color flow mapping after cardiac transplantation

Abstract Color-coded Doppler echocardiography permits visualization of the spatial distribution of flow velocities produced by valvular regurgitation with a high sensitivity. 1 Doppler color flow mapping has been used for simple noninvasive assessment of the magnitude of aortic and mitral regurgitation, and a reasonable agreement between the angiographically estimated grade of aortic or mitral regurgitation and Doppler color flow variables has been reported. 1–3 Doppler color flow mapping is a sensitive and specific technique in detecting tricuspid regurgitation. 4 However, little is known about the assessment of the magnitude of tricuspid regurgitation by color Doppler flow imaging, probably because a reliable reference standard for the assessment of tricuspid regurgitation is lacking. Therefore, we compared various measurements derived from the color Doppler flow imaging with the tricuspid regurgitant fraction obtained by a double thermodilution technique. The study group consisted of cardiac transplant patients who are known to have a high incidence of tricuspid regurgitation without any other valve abnormalities. 5,6