Anomalous pulmonary vein connection.
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Cardiac Catheterization↗
Biomedical subjects
P Held
Publications and source records attributed to P Held.
Randomized trial of candesartan cilexetil in the treatment of patients with congestive heart failure and a history of intolerance to angiotensin-converting enzyme inhibitors.
BACKGROUND: Many patients with congestive heart failure do not receive the benefits of angiotensin-converting enzyme (ACE) inhibitors because of intolerance. We sought to determine the tolerability of an angiotensin II receptor blocker, candesartan cilexetil, among patients considered intolerant of ACE inhibitors. METHODS: Patients with CHF, left ventricular ejection fraction less than 35%, and history of discontinuing an ACE inhibitor because of intolerance underwent double-blind randomization in a 2:1 ratio to receive candesartan (n = 179) or a placebo (n = 91). The initial dosage of candesartan was 4 mg/d; the dosage was increased to 16 mg/d if the drug was tolerated. A history of intolerance of ACE inhibitor was attributed to cough (67% of patients), hypotension (15%), or renal dysfunction (11%). RESULTS: The study drug was continued for 12 weeks by 82.7% of patients who received candesartan versus 86.8% of patients who received the placebo. This 4.1% greater discontinuation rate with active therapy was not significant; the 95% confidence interval ranged from 4.8% more discontinuation with placebo to 13% more with candesartan. Titration to the 16-mg target dose was possible for 69% of patients who received candesartan versus 84% of those who received the placebo. Frequencies of death and morbidity were not significantly different between the candesartan and placebo groups (death 3.4% and 3.3%, worsening heart failure 8.4% and 13.2%, myocardial infarction 2.8% and 5.5%, all-cause hospitalization 12.8% and 18.7%, and death or hospitalization for heart failure 11.7% and 14.3%). CONCLUSIONS: Candesartan was well tolerated by this population. The effect of candesartan on major clinical end points, including death, remains to be determined.
Aged↗
[3D CISS, 3D MP-PAGE and 2D TSE for the preoperative MRI prior to cochlear implantation].
PURPOSE: The aim of this study was to determine the presurgical predictive value of high resolution MRI in patients scheduled for cochlear implantation. METHOD AND MATERIAL: The presurgical MRI (3D CISS, 3D MP-RAGE with and without i.v. contrast medium, 2D TSE) findings of 54 patients and the intraoperative situation reported by the surgeon were compared retrospectively. The surgical and functional success of the cochlear implantation was evaluated. RESULTS: We found a high degree of correlation between MRI and intraoperative findings concerning the patency of the whole cochlea and anomalies as well as in the diagnosis of pathology of the cochlear, vestibular and facial nerves and in anomalies of the internal auditory canal. However, in four out of 54 patients there was a false negative prediction regarding the patency of the cochlea. The sensitivity was 50% (4/8), the specificity 100% (46/46). Concerning the surgical success the accuracy was 100%. In all patients MRI gave sufficient anatomical information to the surgeon concerning the jugular bulb and the facial nerve. CONCLUSION: A high-resolution MRI protocol consisting of coronal 2D T2w TSE, 3D T2*w transverse CISS; plain and contrast enhanced sagittal T1w 3D MP-RAGE is recommended for the evaluation of candidates scheduled for cochlear implantation.
Adolescent↗
Reduction of motion artifacts in magnetic resonance imaging of the neck and cervical spine by long-term averaging.
RATIONALE AND OBJECTIVES: We performed a prospective comparison of T1-weighted turbo spin-echo (TSE) imaging with standard averaging and with the long-term averaging method (LOTA), comparing the effects on signal-to-artifact noise ratio (S/aN) and motion artifacts. METHODS: In 30 consecutive patients undergoing imaging of the neck or cervical spine, a transverse T1-weighted TSE sequence was applied with and without LOTA by using identical sequence parameters. Quantitative image analysis was done by calculating S/Ns in the phase-encoding direction (S/aN). Visual image analysis was performed by four independent, masked readers using a standardized score sheet for anatomic and pathological findings. RESULTS: The LOTA sequence yielded significantly superior S/aN values compared with the standard averaging sequence. In the subjective evaluation, the LOTA sequence showed significantly fewer motion artifacts and better visualization of normal anatomy of the neck, cervical spine, and spinal cord, as well as of the pathological findings. CONCLUSIONS: LOTA is a valuable method for increasing S/aN in magnetic resonance imaging of the neck and cervical spine. It reduces motion artifacts and increases the conspicuity of pathology without increasing acquisition time. No additional hardware is needed, and this technique can be combined with other artifact-reducing methods.
Adult↗
The safety and tolerability of candesartan cilexetil in CHF.
The management of congestive heart failure (CHF) continues to represent a major therapeutic challenge. The primary goal of any treatment is the improvement of symptoms with a reduction in CHF related morbidity and a neutral or beneficial effect on mortality. The number of hospitalisations is considered an important measure of morbidity and quality-of-life in these patients. This pooled safety analysis was performed on adverse event data from five placebo-controlled studies involving a total of 1893 patients, 1287 of whom received candesartan cilexetil and 606 of whom received placebo. These were the only placebo-controlled phase II and III studies of candesartan safety available at the time of the analysis, and investigated the efficacy and safety of candesartan cilexetil in patients with CHF. None was designed as an endpoint trial. A blinded, independent review of all adverse event data was performed to assess all-cause mortality and unexpected deaths, and hospitalisations for acute deterioration of CHF, chronic progression of CHF, other intercurrent events, or accidental injury/attempted suicide. The descriptive analysis included crude and cumulative incidence rates for mortality and cardiac and non-cardiac morbidity using the Kaplan-Meier method and the log-rank test. The sample population was predominantly (approximately two thirds) male, with a median age of 61 years (range: 20-89 years). The median age for women in the sample population was 66 years (range: 26-86 years). Patients received candesartan cilexetil, 2-32 mg, over a median period of 84 days (range: 1-418 days), or placebo over a median period of 85 days (range: 1-398 days). The results demonstrated a clinically non-significant trend for all relevant events (deaths and hospitalisations, whether related to CHF or not) to occur less frequently in patients receiving candesartan cilexetil than in patients receiving placebo (deaths - candesartan cilexetil: 1.6%, placebo: 1.8%; hospitalisations - candesartan cilexetil: 7.2%, placebo: 10.9%). There was a significant treatment difference in CHF hospitalisations (candesartan cilexetil: 3.0% vs. placebo: 5.6%). The time to event analysis revealed that significantly fewer hospitalisations due to CHF occurred in the group receiving candesartan cilexetil than in the group receiving placebo. This treatment difference persisted throughout therapy (log-rank test; p < 0.028). These results show the safety of candesartan cilexetil, compared with placebo, in the treatment of patients with CHF.
Adult↗
MRI detection of olfactory bulb and tract.
Thirty healthy volunteers underwent MRI with 3D MP-RAGE, 3D CISS and 2D turbo spin echo sequences to compare the detectability of olfactory fibers, bulb, tract, and sulcus. The overall detectability was slightly better using MP-RAGE compared with CISS. Both 3D sequences were superior to 2D turbo spin echo. We therefore recommend including the MP-RAGE sequence in an MR imaging protocol of the olfactory nerve.
Adolescent↗
Comparison of a T2* w. 3D CISS and a T2 w. 3D turbo spin echo sequence for the anatomical study of facial and vestibulocochlear nerves.
Thirty healthy volunteers were examined with a T2* w. 3D CISS and a T2 w. 3D turbo spin echo (TSE) sequence in order to compare the facial and vestibulocochlear nerve detectability in the cerebellopontine angle and the internal auditory canal. CISS was significantly better than 3D TSE for nerve detectability in the cerebellopontine angle and equally as good as 3D TSE in the internal auditory canal. We would therefore recommend the inclusion of CISS in an MR imaging protocol of the facial and vestibulocochlear nerves.
Adolescent↗
Effects of digoxin on electrocardiogram in patients with acute atrial fibrillation--a randomized, placebo-controlled study. Digitalis in Acute Atrial Fibrillation (DAAF) Trial Group.
BACKGROUND: Studies of healthy volunteers or patients in sinus rhythm have indicated that treatment with digoxin produces characteristic changes in the electrocardiogram (ECG). No randomized, placebo-controlled studies are available and no study has investigated the effect on ECG in patients with atrial fibrillation. HYPOTHESIS: In a substudy to a trial comparing the therapeutic effect of intravenously administered digoxin with placebo in patients with acute atrial fibrillation, we investigated these effects as well as the relation between ECG changes and serum concentration of digoxin. METHODS: In all, 167 patients were included. Standard ECGs recorded at baseline, and at 2, 6, 12, and 16 h after randomization were digitized, and changes in RR-intervals, QRS width, ST-segment amplitude at 60 ms after the J point, T-wave amplitude, and QTc interval were calculated. Furthermore, the correlation between the serum concentration of digoxin at 16 h after inclusion and changes on the ECG was analyzed. RESULTS: Compared with placebo, digoxin resulted in an increase in RR-interval (p < 0.0001), a decrease in ST-segment and T-wave amplitude (p = 0.009 and p = 0.002, respectively), and in the QTc interval (p = 0.01). These changes were present 2 h after the first dose, but were more pronounced after 16 h. There was no significant correlation between serum concentration of digoxin and ECG changes at 16 h. CONCLUSION: Compared with placebo, digoxin produces significant changes on ECG in patients with acute atrial fibrillation. The changes are in accordance with previous findings in individuals in sinus rhythm. There was no correlation between serum concentration of digoxin and ECG changes.
Acute Disease↗
Somatostatin receptor scintigraphy in thymoma imaging method and clinical application.
Somatostatin receptor scintigraphy with 111In-[DTPA-D-Phe1]-octreotide has the potential for visualizing primary and recurrent thymomas in patients with myasthenia gravis, whereas thymic hyperplasias fail to accumulate somatostatin analog peptides. We demonstrate somatostatin receptor imaging findings in a patient with a mixed encapsulated thymoma which exhibited intense 111In-[DTPA-D-Phe1]-octreotide uptake in early and late scans. In another patient with a history of malignant thymoma 111In-[DTPA-D-Phe1]-octreotide accumulation was clearly seen in a mass suspected to be a recurrence. This paper describes the imaging protocol including Single Photon Emission Computed Tomography (SPECT) and discusses the clinical applications of this feasible functional imaging method in patients with thymomas.
Female↗
The value of T2(*)-weighted MR images for the diagnosis of acoustic neuromas.
UNLABELLED: The aim of this study was to evaluate high resolution T2(*)-weighted MRI--in our case a 3D CISS sequence--for the diagnosis of acoustic neuromas. Especially to be clarified was if high-resolution T2-weighted sequences can substitute T1-weighted contrast-enhanced sequences, and in which circumstances they can give important additional information when compared with contrast-enhanced T1-weighted sequences. METHODS AND PATIENTS: The MR examinations were performed using a 1.5-Tesla unit with a circularly polarized head coil. All 20 patients (11 females, nine males, aged from 12 to 80 years) with acoustic neuromas underwent preoperative MRI with T2*-weighted 3D CISS (slice thickness, 0.7 mm; acquisition time, 8 min) and pre- and postcontrast T1-weighted 3D MP-RAGE (slice thickness, 0.9 mm; acquisition time, 8 min) sequences. The detectability of acoustic neuromas was evaluated following the consensus of three radiologists using a 3D work station (parameters: tumor presence, extent, nerve attribution). RESULTS: All tumors were detected by both contrast-enhanced 3D MP-RAGE and 3D CISS and the diameters of the lesions were equally well measured. 3D CISS was the best sequence for the attribution of a lesion to a certain nerve. Labyrinthine involvement could be better detected using 3D CISS than contrast-enhanced 3D MP-RAGE. CONCLUSION: High-resolution T2(*)-weighted MRI is a very sensitive method for tumor screening which can also detect even small meatal and labyrinthine neuromas. In the case of abnormal findings (other pathology or variations, e.g. vascular loops); however, contrast-enhanced T1-weighted MRI is necessary in order to confirm the presence of a tumor with typical enhancement.
Adult↗
Candesartan in heart failure--assessment of reduction in mortality and morbidity (CHARM): rationale and design. Charm-Programme Investigators.
BACKGROUND: Chronic heart failure (CHF) is an increasing burden to health care. Pharmacological treatment with angiotensin-converting enzyme (ACE) inhibitors and beta blockers improve survival and reduce hospitalizations in patients with low left ventricular ejection fraction (LVEF). Despite these therapies, morbidity and mortality remains problematic. Furthermore, 30% to 50% of patients with CHF have a preserved LVEF. It is not known if treatments are of benefit in this group. DESIGN: Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity (CHARM) is a program designed to investigate the clinical usefulness of the long-acting angiotensin II type 1 receptor blocker, candesartan cilexetil, in a broad spectrum of patients with symptomatic heart failure. Patients with systolic dysfunction, tolerant or intolerant to an ACE-inhibitor, and patients with preserved systolic function are included. Specifically, the CHARM program consists of 3 independent, parallel, placebo-controlled studies in patients with (1) LVEF less than or equal to 40%, ACE-inhibitor treated (n = 2,300); (2) LVEF less than or equal to 40%, ACE-inhibitor intolerant (n = 1,700); (3) LVEF greater than 40%, not treated with ACE inhibitors (n = 2,500). The 3 studies will be combined to evaluate the effect of candesartan cilexetil on all-cause mortality in the broad spectrum of symptomatic heart failure. The primary objective in each trial is to evaluate the effects on the combined endpoint of cardiovascular mortality or CHF hospitalization. Other endpoints include the effects on myocardial infarction, all-cause hospitalization, and resource utilization. CHARM is intended to randomize 6,500 patients with symptomatic heart failure from 26 countries in Europe, the United States, Canada, South Africa, and Australia. The CHARM program started to enroll patients in March 1999. The follow-up period is a minimum of 2 years. The study is expected to end in the third quarter of 2002.
Adolescent↗
Contemporary management of patients with left ventricular systolic dysfunction. Results from the Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry.
AIMS: The reported prevalence of angiotensin-converting enzyme (ACE) inhibitor use in patients with heart failure varies considerably. Recent reports suggest that many patients who could benefit from such therapy are not receiving ACE inhibitors. The Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry was established to understand better the demographics, characteristics, and contemporary use of ACE inhibitors in an international registry. METHODS AND RESULTS: Between August 1996 and April 1997, each of 105 study centres from eight countries in North America and Europe was invited to review retrospectively the medical records of 100 consecutive patients with left ventricular ejection fractions </=35%. The median age of the 9580 Registry patients was 66 years, 26% were women, the median ejection fraction was 27%, and the primary aetiology of left ventricular dysfunction was ischaemic (63%). Eighty percent of patients were receiving ACE inhibitors. The most common reason for non-use of ACE inhibitors was intolerance (9%). CONCLUSION: The SPICE Registry provides a contemporary description of the demographics and management of patients with documented left ventricular systolic dysfunction. The contemporary use of ACE inhibitors (80%) appears to be higher than previously reported and the main reason for non-use is perceived intolerance (9%).
Aged↗
Pharmacokinetics and pharmacodynamics of melagatran, a novel synthetic LMW thrombin inhibitor, in patients with acute DVT.
Forty-eight patients with acute proximal deep vein thrombosis (DVT) were randomised to intravenous infusions for 4 to 6 days with melagatran, a novel synthetic low molecular weight thrombin inhibitor, or unfractionated heparin adjusted by the activated partial thromboplastin time (APTT). The aim of the study was to investigate the pharmacokinetics, pharmacodynamics and the safety of melagatran therapy at three different doses. Steady-state plasma concentrations were rapidly achieved and maintained throughout the infusion period. The mean plasma concentrations in the low, medium and high dose groups were 0.17, 0.31 and 0.53 micromol/l, respectively. The prolongation of APTT was stable during the melagatran infusions and correlated to the plasma concentration. Phlebographically verified regression of thrombus size measured as decrease in Marder score was seen after 4 to 6 days in 8 of 12 patients, 6 of 12 patients and 5 of 11 patients in the low, medium and high dose groups of melagatran and in 5 of the heparin-treated patients. In the low dose group with melagatran, thrombus extension was seen in one patient. At the dose levels studied, melagatran was well tolerated with no clinically significant bleeding problems, suggesting that melagatran could safely be given to patients suffering from DVT.
Adolescent↗
Functional MR imaging of the motor cortex in healthy volunteers and patients with brain tumours: qualitative and quantitative results.
The purpose of this study was to compare functional magnetic resonance (MR) imaging of the motor cortex in healthy volunteers and patients with brain tumours. Functional MR imaging was performed in 14 healthy volunteers and 14 patients with tumours in or near the primary motor cortex with groups being matched for age, sex, and handedness. Functional images were acquired during motion of the right and left hand. Time courses of signal intensity within the contralateral, ipsilateral, and supplementary motor cortex as well as z-maps were calculated, their quality being assessed visually. Mean signal increase between activation and rest were evaluated within the contralateral, ipsilateral, and supplementary motor cortex, the activated area in those regions of interest was measured using z-maps. The quality of functional MR experiments was generally lower in patients than in volunteers. The quantitative results showed a trend towards increased ipsilateral activation in volunteers during left hand compared to right hand motion and in patients during motion of the affected compared to the non-affected hand. Considering quantitative and qualitative results, significantly increased ipsilateral activation was found in patients compared to healthy volunteers. In conclusion, functional MR imaging quality was significantly reduced in patient studies compared to healthy volunteers, even if influences of age, sex, and handedness were excluded. Increased ipsilateral activation was found in patients with brain tumours which can be interpreted by an improved connectivity between both hemispheres.
Adult↗
[Cardiac metastasis of a plasmacytoma with clinical manifestations of an extensive pulmonary embolism. Obstruction of the right ventricular outflow tract].
HISTORY AND CLINICAL FINDINGS: A 48-year-old man with advanced light-chain plasmacytoma was admitted because of severe dyspnoea and tachycardia. Physical examination revealed peripheral cyanosis and signs of right heart failure. INVESTIGATIONS: The partial pressure of oxygen and CO2 in arterial blood were both reduces (72 mm Hg and 33 mm Hg, respectively). Liver enzyme activities were increased, there was right heart enlargement radiologically and the ECG showed low voltage and typical signs of right heart strain. Echocardiography revealed cardiac metastases of the plasmacytoma with subtotal right ventricular outflow tract obstruction (RVOTO), without any signs of pulmonary emboli. TREATMENT AND COURSE: Palliative radiotherapy to the heart reduced the intracardiac tumor size and improved the patients' general condition. The signs of the RVOTO were markedly reduced in both the ECG and the echocardiogram. But after this initial improvement pneumonia developed, of which the patient died. Autopsy revealed radiation pneumonia with extensive fibrosis as the immediate cause of death. CONCLUSION: In patients with advanced neoplasia cardiac metastasis should be included in the differential diagnosis of dyspnoea, tachycardia or hypotension of uncertain etiology. Echocardiography is the diagnostic tool of choice.
Blood Gas Analysis↗
Ligand- and DNA-induced dissociation of RXR tetramers.
Unliganded bacterially expressed RXR alpha lacking the N-terminal region AB (apo-RXR alpha delta AB) was found in solution as an apparent mixture of 165 kDa tetramers and 42 kDa monomers which could be quantitatively separated by gel filtration and non-denaturing gel electrophoresis. Under identical conditions both liganded (holo-) and apo-RAR alpha delta AB were present as single monomeric species. apo-RXR alpha delta AB tetramers, as well as dimers of the apo-RXR ligand binding domain (apo-LBD), dissociated readily into monomers when exposed to their cognate ligand 9-cis retinoic acid (9c-RA). The apo-RXR alpha delta AB tetramer bound only transiently to a cognate DR1 response element, and was converted into DR1-apo-RXR alpha delta AB homodimer complexes indistinguishable from those generated by cooperative DNA binding of apo-RXR alpha delta AB monomers. In the absence of DNA, the addition of 9c-RA greatly accelerated the formation of heterodimers with the apo-RAR alpha delta AB heterodimerization partner. No RXR alpha delta AB or RAR alpha delta AB homodimers could be observed in solution, but upon mixing of the two receptor monomers stable heterodimers could be isolated which bound to DR5 response elements in a highly cooperative manner. In these heterodimers, RXR alpha delta AB interacted with its cognate ligand as efficiently as in RXR alpha delta AB homodimers. The presence of ligand did not alter the stability of RXR alpha delta AB homodimer or RXR alpha delta AB-RAR alpha delta AB heterodimer complexes on DR1 and DR5 response elements, respectively. These in vitro data support a model in which RXR tetramers could serve as an inactive pool with the dual function of: (i) rapidly supplying large amounts of RXR heterodimerization partners upon 9c-RA generation; and (ii) allowing RXR homodimer formation on "accessible" cognate response elements in the absence of 9c-RA. These events may represent a ligand-dependent regulatory mechanism controlling the availability of the promiscuous RXR dimerization partner that is engaged in multiple nuclear receptor signalling pathways.
Amino Acid Substitution↗
N-terminal proANF in acute atrial fibrillation: a biochemical marker of atrial pressures but not a predictor for conversion to sinus rhythm. Digitalis in Acute Atrial Fibrillation (DAAF) Trial group.
BACKGROUND: Atrial filling pressures are increased in acute atrial fibrillation, which stimulates the release of atrial natriuretic factor pro-hormone, proANF. METHODS: In a randomized trial comparing digoxin with placebo in 216 patients, we investigated whether the baseline plasma level of N-terminal proANF is a predictor for conversion to sinus rhythm and the relation among N-terminal proANF, conversion to sinus rhythm, and changes in heart rate. RESULTS: N-terminal proANF was increased at baseline and decreased significantly in patients converting to sinus rhythm, whereas it was mainly unchanged in nonconverters. N-terminal proANF was not a predictor of conversion to sinus rhythm. A relation was found between relative changes in heart rate and N-terminal proANF in nonconverters. CONCLUSION: The level of N-terminal proANF does not predict conversion to sinus rhythm, which indicates that hemodynamics per se is not important. There is a correlation between relative changes in heart rate and N-terminal proANF in nonconverters.
Acute Disease↗
To screen or not to screen: how to improve clinical trials.
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Cardiovascular Diseases↗