Rydberg-resolved resonant inelastic soft x-ray scattering: dynamics at core ionization thresholds.

Resonant inelastic x-ray scattering spectra excited in the immediate vicinity of the core-level ionization thresholds of N2 have been recorded. Final states of well-resolved symmetry-selected Rydberg series converging to valence-level ionization thresholds with vibrational excitations are observed. The results are well described by a quasi-two-step model which assumes that the excited electron is unaffected by the radiative decay. This threshold dynamics simplifies the interpretation of resonant inelastic x-ray scattering spectra considerably and facilitates characterization of low-energy excited final states in molecular systems.

Pectus excavatum: echocardiography and cardiac MRI reveal frequent pericardial effusion and right-sided heart anomalies.

AIMS: In patients with pectus excavatum (PEX), echocardiographic assessment can be difficult. There are little data on the impact of the chest deformity on echocardiographic findings and comparison of data obtained by echocardiography (echo) with cardiac magnetic resonance imaging (CMR) in PEX. METHODS AND RESULTS: In a prospective study, cardiac anomalies in PEX were analysed by echo and compared with CMR in consecutive patients with PEX referred for echo. If they agreed to participate, the patients were referred for CMR and included if the pectus index was ≥3.0 by CMR. Also, clinical data and electrocardiogram tracings were analysed. There were 18 patients (13 females; 72%), with a mean age of 53±16 years; mean pectus index was 4.7 (range: 3-7.3). Echo showed haemodynamically insignificant pericardial effusion in six patients (33%), tricuspid valve prolapse in five (28%), right ventricular (RV) localized wall motion anomalies (WMA) in five (28%) and diminished RV systolic function in two (11%); no patient had RV dilatation. CMR demonstrated cardiac displacement to the left in 9 patients (50%); minimal pericardial effusion was seen in 10 patients (56%; P value=0.13 compared with echo), RV localized WMA in 6 (44%; P value=1.0), diminished RV systolic function in 8 (44%; P=0.07), and RV dilatation in 5 (28%; P=0.06). A completely normal cardiac examination was found in six patients by echo (33%) and in 2 (11%) using CMR. Although some signs of arrhythmogenic RV cardiomyopathy (ARVC) were present, no patient fulfilled the ARVC criteria. CONCLUSION: In severe PEX, haemodynamically insignificant pericardial effusion, tricuspid valve prolapse and other RV anomalies possibly due to RV displacement are frequent as demonstrated by both CMR and echo. The cardiac assessment by echo and CMR did show discrepancies; however, they were not significant.

N-terminal pro-brain natriuretic peptide used for the prediction of coronary artery stenosis.

BACKGROUND: The level of the inactive N-terminal fragment of pro-brain (B-type) natriuretic peptide (NT-proBNP) is a prognostic marker in patients with acute and chronic coronary artery disease (CAD). It might also be valuable for non-invasive diagnosis of coronary artery disease. MATERIALS AND METHODS: The NT-proBNP was measured in 781 consecutive patients with normal left ventricular function referred for coronary angiography owing to symptoms or signs of CAD. The diagnostic value of NT-proBNP was assessed for predicting CAD at angiography. RESULTS: Elevated NT-proBNP levels were associated with the extent of CAD and with the female sex (P < 0.001). The ability of NT-proBNP to predict significant coronary disease at angiography was assessed separately for men using a cut-off point of 85 pg mL(-1), positive likelihood ratio 2.2 (95% CI, 1.7-3.0), negative likelihood ratio 0.53 (95% CI 0.45-0.63) and area under the receiver-operating-characteristic (ROC) curve 0.72: for women, it was assessed using a cut-off point of 165 pg mL(-1), positive likelihood ratio 2.4 (95% CI, 1.7-3.4), negative likelihood ratio 0.55 (95% CI, 0.44-0.70) and area under ROC curve 0.71. In multiple logistic-regression analysis, NT-proBNP added significant independent predictive power to other clinical variables in models predicting CAD (odds ratio 2.76, 95% CI, 1.76-4.32, P < 0.001). CONCLUSIONS: The NT-proBNP is a marker of non-obstructive CAD and of significant coronary stenosis. In conjunction with other clinical information, measurement of NT-proBNP with the use of sex-specific reference ranges may improve the non-invasive prediction of CAD.

[Coffee--poison or medicine?]. / Kaffee--Gift oder Medizin?

Intake of coffee, one of the most common beverages worldwide, has often been discussed as a potential cardiovascular risk factor. However, definitive data about this topic are missing and newer studies even point out for a favorable rather than hazardous effect. Despite many studies no clear association between coffee and the risk of hypertension, myocardial infarction and other cardiovascular diseases was found. Recent publications suggest that moderate coffee intake does not represent a health hazard, but may even be associated with beneficial effects on the cardiovascular system and diabetes.

[ICD therapy in patients with coronary artery disease--incidence of adequate interventions]. / ICD-therapie bei Patienten mit koronarer Herzkrankheit--Inzidenz adäquater Interventionen.

BACKGROUND: The Implantable Cardioverter/Defibrillator (ICD) represents the therapy of choice for patients at risk of malignant ventricular arrhythmias. The survival benefit of the ICD vs antiarrhythmic therapy in patients with coronary artery disease and ventricular tachycardia has been proven. Recently, the ICD therapy has also been established for primary prevention in high risk patients. We report about the incidence of adequate ICD therapies in patients with coronary artery disease, who underwent ICD implantation at the University Hospital Zurich. METHODS: 104 consecutive patients (97 men, 7 women, mean age of 67 +/- 10 years) with coronary artery disease, who underwent ICD implantation in accordance with the AHA/ACC/NASPE guidelines between January 2000 and July 2003 were included in the study. Follow-up was performed every three to six months, when all ICD therapies were documented. This documentation was used for analysis of adequate or inadequate ICD therapies. RESULTS: The mean follow-up time was 383 +/- 195 days. The time to the first adequate therapy was 201 +/- 283 days. The cumulative incidence for the first adequate therapy was 21% at six months, 39% at two years and 59% at four years. In 64% of patients, who experienced adequate ICD therapies, antitachycardia pacing (ATP) and in 36% an initial shock was delivered. ATP was successful in 83% of adequately delivered episodes. In the follow-up period 12 patients died. CONCLUSION: The benefit of the ICD was apparent in patients at risk for ventricular arrhythmias and coronary artery disease after a relatively short period of time, which underlines the important role of the ICD in primary and secondary prevention.

[Psychopharmaceuticals and arrhythmias]. / Psychopharmaka und Herzrhythmusstörungen.

Psychoactive drugs have been associated with arrhythmia for 40 years. Torsades de pointes was originally seen in patients with pre-existing heart disease or with intoxication. Now, there is increasing awareness that drugs used for non-antiarrhythmic and non-cardiovascular indications can exert significant effects on repolarisation and may cause ventricular tachycardia. Most of the drugs that prolong the QT-interval incorporate blockade of the potassium channel Ikr in their spectrum. Among psychotrophic drugs the low-potency phenothiazines have most often been implicated, particularly thioridazine. For the high-potency phenothiazines and butyrophenones there are fewer reports on serious arrhythmia. More recently the atypical antipsychotics have been introduced. Although some of them increase the QT-interval considerably arrhythmic events seem to be a very rare problem with the atypical antipsychotics available. Drugs acting as class I antiarrhythmics such as tricyclic antidepressants are not recommended after myocardial infarction. Selective serotonin reuptake inhibitors seem to be safe. Patients with a prolonged QT-interval or patients that experienced Torsade de pointes are at a considerable higher risk upon exposition to a QT-prolonging drug. Drug interactions played a role in many fatalities with QT-prolonging drugs and are important.

[Stress, depression and cardiac arrhythmias]. / Stress, Depression und kardiale Arrhythmien.

A relationship between behavioural factors and cardiac arrhythmogenesis in humans has been described. Three sets of conditions contribute to the occurrence of arrhythmias: myocardial electrical instability, most often due to coronary artery disease; an acute triggering event, frequently related to mental stress; and a chronic, pervasive, and intense psychological state, often including depression and hopelessness. The autonomic nervous system plays an important role in the occurrence of cardiac arrhythmias and it is well documented that mood alterations as mental stress and depression influence cardiac autonomic balance. There is an increasing body of evidence that patients with the greatest changes in cardiac neural regulation with decreased parasympathetic tone coupled with increased sympathetic activity are at the greatest risk for developing fatal ventricular arrhythmias. These patients have a reduced heart rate variability, increased QT-dispersion and a decreased baroreceptor sensitivity. The influence of stress and depression on the autonomic nervous system and the impact on the occurrence of both atrial and ventricular arrhythmias is being discussed.

Predictors of long-term survival after valve replacement for chronic aortic regurgitation; is M-mode echocardiography sufficient?

AIMS: The clinical importance of pre-operative and follow-up echocardiographic studies in patients operated on for chronic severe aortic valve regurgitation is still a matter of debate. The prognostic significance of M-mode echocardiography has never been directly compared with clinical and angiographic data. METHODS AND RESULTS: Univariate and multivariate analyses of cumulative survival were performed for clinical, echocardiographic and angiographic data of 125 patients operated on between 1975 and 1983, and followed for 13.3+/-6.4 years. Ten and 20 year survival rates were 77% and 48%, respectively. Age, NYHA class, angiographic volumes, ejection fraction, as well as M-mode echocardiographic end-systolic dimension and shortening fraction were the main pre-operative prognostic parameters for long-term survival. In a multivariate analysis the angiographic end-systolic volume index, age and preoperative NYHA class were independent pre-operative prognostic variables of long-term survival. A postoperative reduction in end-diastolic dimension of >20% predicted a significantly better late survival (74% vs 44% after 20 years, P<0.001). CONCLUSIONS: Age, pre-operative NYHA class and left ventricular systolic function are the main determinants of long-term survival after valve replacement for chronic aortic regurgitation. Despite a slightly lower predictive value of echocardiography when compared to angiography, it appeared sufficient for everyday clinical decision making for valve replacement. Echocardiography within 6 months postoperatively is able to detect recovery of left ventricular function, and enables additional risk-stratification, regardless of pre-operative findings.

Systemic, pulmonary, and renal hemodynamic effects of endothelin ET(A/B)-receptor blockade in patients with maintained left ventricular function.

Endothelin-1 (ET-1) regulates vascular tone in congestive heart failure and modulates renal function. Its role in patients with normal left ventricular (LV) function and its renal effects are unclear. Cardiac and renal hemodynamics were studied in 24 patients with normal LV function and coronary arteries after single-dose, double-blind, randomized administration of TAK-044 (25, 50, or 100 mg, i.v.), an ET(A/B)-receptor antagonist, or placebo. Hemodynamics were monitored using Swan-Ganz and arterial catheters, and ET levels were measured. Renal function was assessed by clearance techniques. In the absence of a dose-response relation, TAK-044 patients were analyzed as a single group. Most hemodynamic effects occurred during the first 4 h. TAK-044 reduced mean arterial (-9.3 mm Hg, p < 0.001), pulmonary (-1.8 mm Hg, p = 0.01), and pulmonary capillary wedge pressure (-1.6 mm Hg, p < 0.001) between 30 min and 4 h. Mean reduction in systemic vascular resistance was 279 dyne/s/cm2 (p < 0.001), whereas heart rate increased 6.1 beats/min (p < 0.001) and cardiac index by 0.37 L/m2 (p = 0.01). Stroke volume index, right atrial pressure, and pulmonary vascular resistance did not change. TAK-044 increased renal plasma flow in proportion to the increase in cardiac output (+119 ml/min, 4 h after TAK-044; p < 0.05) and ET-1 levels (2.5-fold; p < 0.05). No serious side effects were noted. In patients with normal cardiac function, ET-receptor blockade causes vasodilation and reduces systemic but not pulmonary vascular resistance and increases cardiac index and renal plasma flow.

Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans.

OBJECTIVES: We sought to investigate baroreceptor regulation of sympathetic nerve activity and hemodynamics after inhibition of nitric oxide (NO) synthesis. BACKGROUND: Both the sympathetic nervous system and endothelium-derived substances play essential roles in cardiovascular homeostasis and diseases. Little is known about their interactions. METHODS: In healthy volunteers, we recorded muscle sympathetic nerve activity (MSA) with microneurography and central hemodynamics measured at different levels of central venous pressure induced by lower body negative pressure. RESULTS: After administration of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min), systolic blood pressure increased by 24 mm Hg (p = 0.01) and diastolic blood pressure by 12 mm Hg (p = 0.009), while stroke volume index (measured by thermodilution) fell from 53 to 38 mL/min/m2 (p < 0.002). Administration of L-NMMA prevented the compensatory increase of heart rate, but not MSA, to orthostatic stress. The altered response of heart rate was not due to higher blood pressure, because heart rate responses were not altered during infusion of the alpha-1-adrenoceptor agonist phenylephrine (titrated to an equal increase of systolic blood pressure). In the presence of equal systolic blood pressure and central venous pressure, we found no difference in MSA during phenylephrine and L-NMMA infusion. CONCLUSIONS: This study demonstrates a highly specific alteration of baroreceptor regulation of heart rate but not muscle sympathetic activity after inhibition of NO synthesis in healthy volunteers. This suggests an important role of NO in reflex-mediated heart rate regulation in humans.

Autonomic nervous system-controlled cardiac pacing: a comparison between intracardiac impedance signal and muscle sympathetic nerve activity.

A recently introduced rate responsive cardiac pacing system is based on information derived from the intracardiac impedance signal containing information on the inotropic state of the ventricle. This study compared the inotropic state index (ISI) with muscle sympathetic activity (MSA), both being modulated by the autonomic nervous system. Nine patients (66 +/- 3 years, mean +/- SEM) with Inos2DR pacemakers were included. Each patient was studied at rest and during cold pressor test (CPT). Microneurography of the peroneal nerve was performed to measure MSA continuously, which was digitally stored along with continuous surface ECG and blood pressure. The intracardiac impedance signal was transmitted by the pacemaker and stored simultaneously. Linear correlation between ISI and MSA was calculated for the period of the CPT. During CPT, mean systolic blood pressure increased from 122 +/- 4 to 149 +/- 6 mmHg (P < 0.0001), diastolic blood pressure increased from 74 +/- 8 to 86 +/- 4 mmHg (P = 0.02), and intrinsic heart rate increased from 69 +/- 7 to 75 +/- 7 beats/mill (P = 0.019). ISI increased by 21 +/- 7% (P = 0.018), MSA by 26 +/- 6% (P = 0.004). ISI and MSA were positively correlated during the CPT in eight of nine patients (R2 = 0.86-0.99, P < 0.0001). Negative correlation was found in one patient (R2 = 0.94). This study demonstrates parallel increases of the ISI and MSA during CPT. ISI and MSA showed a close linear relationship during provoked changes of sympathetic activity. These results provide further evidence that the sympathetic nervous system is responsible for the observed ISI changes.

Role of sympathetic nervous system in hypertension and effects of cardiovascular drugs.

The sympathetic nervous system (SNS) plays an important role in the regulation of cardiac performance and peripheral circulation. Changes in SNS activity measured as catecholamines in plasma or organ spillover have been implicated in the pathogenesis of hypertension. Recent studies using microneurography to directly assess peripheral sympathetic nerve activity have demonstrated an increase in sympathetic activity in patients with borderline hypertension at rest and during hypoxia. We have recently shown that resting muscle sympathetic nerve activity is comparable in offspring of hypertensive and normotensive parents. However, during mental arithmetic the increase in muscle sympathetic nerve activity and blood pressure was significantly more pronounced in offspring of hypertensive than in offspring of normotensive parents, but resting blood pressure was in the normotensive range and comparable in both groups. These data indicate that the response to mental stress results in a more pronounced activation of SNS in normotensive subjects with a genetic background of hypertension. In other cardiovascular disease states such as acute myocardial infarction and heart failure activity of the SNS may determine prognosis significantly. Some calcium antagonists which are successfully used to treat patients with hypertension and stable angina pectoris may have unfavourable effects in patients with impaired left ventricular function. This could be due in part to baroreceptor-mediated activation of the SNS, an effect which seems to be related to pharmacokinetics and pharmacodynamics of the drugs. In contrast, angiotensin converting enzyme inhibitors seem to directly decrease sympathetic nerve activity. This may explain at least in part their beneficial effects in patients with impaired left ventricular function. Thus, the SNS as a regulator of the cardiovascular system also plays an important role in the pathophysiology of cardiovascular diseases such as hypertension, myocardial infarction and heart failure. Furthermore, drug therapy could have a significant impact on the activity of the SNS.

Differential activation of cardiac and peripheral sympathetic nervous system by nifedipine: role of pharmacokinetics.

OBJECTIVES: We sought to study the effects of short-acting and long-acting nifedipine on the sympathetic nervous system (SNS), heart rate (HR) and blood pressure (BP) of normotensive subjects under baseline conditions and during SNS stimulation. BACKGROUND: Calcium channel antagonists in different pharmacokinetic formulations are widely used in patients with coronary artery disease or hypertension. Short-acting formulations activate the SNS, an action that may be disadvantageous in patients with coronary disease, especially if left ventricular function is impaired. The effects of slow-release formulations on the SNS are unknown. METHODS: We used microneurography to investigate the influence of nifedipine (5 mg; 10 mg; and slow-release [GITS], 60 mg) on muscle sympathetic nerve activity (MSA) and skin sympathetic nerve activity (SSA) in healthy volunteers. RESULTS: Peak plasma levels after short-acting and slow-release nifedipine were achieved within 60 min and 330 min, respectively. Short-acting (10 mg, n = 10) and slow-release (n = 10) nifedipine, but not placebo, markedly activated MSA and increased plasma norepinephrine; plasma endothelin increased only with slow-release nifedipine. HR increased after short-acting nifedipine, but not after nifedipine GITS. Nifedipine had no effect on SSA (n = 6). Blockade of cardiac sympathetic activity (with esmolol) led to similar decreases in HR with or without nifedipine, whereas parasympatholysis (with atropine) led to similar increases in HR with or without nifedipine. The cold pressor test markedly increased MSA in all treatment groups and further increased MSA beyond the increase induced by nifedipine. CONCLUSIONS: Nifedipine markedly increased MSA, but not SSA, independently of drug release formulation. In contrast, HR increased with short-acting, but not with slow-release, nifedipine. Therefore, nifedipine activates cardiac and peripheral sympathetic nerves differently depending on pharmacokinetics. These effects of nifedipine may be disadvantageous in cardiac patients with increased sympathetic activity or congestive heart failure, or both.

[Sympathy and heartache: new information on the sympathetic nervous system]. / Mitleid und Herzschmerz: Neues vom Sympathikus.

The sympathetic nervous system is an important regulator of the circulation. Interactions with other regulating systems, e.g. the renin angiotensin system, play important roles. By means of microneurography, sympathetic activity in humans can be assessed directly in the nerve. Insights into the dynamic regulation of the circulation under physiological and pathophysiological conditions are possible. Activation of the sympathetic nervous system in cardiovascular diseases affects course, prognosis, and therapy. Prognosis in heart failure depends on sympathetic activation, which can be decreased by inhibition of angiotensin II synthesis by ACE-inhibitors. In contrast to nitrates, these drugs do not increase sympathetic activity. The sympathetic nervous system is also heavily involved in the pathogenesis of hypertension. Borderline hypertensives and offspring of hypertensive parents show increased sympathetic nerve activities. Investigation of the sympathetic nervous system under physiological and pathophysiological conditions may serve as a basis for new therapeutic strategies.

Increased activation of sympathetic nervous system and endothelin by mental stress in normotensive offspring of hypertensive parents.

BACKGROUND: The pathogenesis of essential hypertension is still uncertain, but genetic factors and the sympathetic nervous system are likely to be involved. Sympathetic nerve activity and hormonal circulatory control mechanisms, however, are affected by blood pressure itself. Hence, early functional changes are best investigated in normotensive subjects at risk to develop hypertension, such as normotensive offspring of hypertensive parents. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSA) was measured in the peroneal nerve of 10 normotensive offspring of parents with essential hypertension and 8 offspring of normotensive parents. Measurements were performed under resting conditions, during a 10-minute period of hypoxia (12.5% O2/87.5% N2) and during a 3-minute mental stress test. The tests were separated by a 30-minute resting period. Plasma samples for determination of norepinephrine and endothelin were collected before and after the tests. Baseline values of MSA were comparable in offspring of hypertensive and normotensive parents. During hypoxia, MSA, heart rate, and norepinephrine and endothelin plasma levels increased in offspring of hypertensive and normotensive parents to a comparable degree, whereas no significant changes in blood pressure and plasma norepinephrine levels were observed in either group. During mental stress, MSA and plasma norepinephrine and endothelin increased only in offspring of hypertensive parents (P < .001 to .01). In parallel, blood pressure increased significantly only in offspring of hypertensive parents (P < .001 to .05) but heart rate increased in both groups (P < .001 to .05). CONCLUSIONS: The activity of the sympathetic nervous system and plasma norepinephrine and endothelin levels are increased during mental stress only in offspring of hypertensive parents, whereas the response to hypoxia was similar in offspring of hypertensive and normotensive parents, suggesting a genetically determined abnormal regulation of the sympathetic nervous system to certain stressful stimuli in offspring of hypertensive parents. This may play a role in the pathogenesis of essential hypertension.

[Sympathetic nervous system and endothelial function in heart failure]. / Sympathisches Nervensystem und Endothelfunktion bei Herzinsuffizienz.

Congestive heart failure is a frequent cardiovascular disease with a poor prognosis in advanced stages. Activation of neurohumoral systems such as the renin-angiotensin system and the sympathetic nervous system as well as impairment of local regulatory mechanisms (i.e. adrenoceptors, endothelial factors) play an important role in the pathogenesis and prognosis of the disease. The increase in peripheral resistance is due to imbalance of vasoconstrictors and vasodilators in favour of the vasoconstrictors and to changes in endothelial function, i.e. impaired production of nitric oxide, increased production of endothelin. Sodium and volume retention as well as the activation of the renin-angiotensin system increase preload. The sympathetic nervous system, which is known to be an independent negative prognostic factor, is activated and interacts with the renin-angiotensin system; however, up to now it is uncertain, whether these pathophysiological findings contribute to the development of congestive heart failure or if they are only secondary phenomena.