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Biomedical subjects

L Rydén

Publications and source records attributed to L Rydén.

At least 19 recordsLinked to original sources

Determination of sentinel lymph node (SLN) status in primary breast cancer by prospective use of immunohistochemistry increases the rate of micrometastases and isolated tumour cells: analysis of 174 patients after SLN biopsy.

AIM: The objective of the present study was to evaluate the prospective use of immunohistochemistry (IHC) for histopathological diagnosis of sentinel lymph node(s) (SLN) in primary breast cancer using stage migration and non-SLN metastases as endpoints in relation to metastatic involvement. METHOD: Serial sectioning and prospective use of IHC were applied to SLN examination in addition to routine haematoxylin-eosin staining in 174 consecutive patients with unifocal T1-T2 breast cancer included in a National Sentinel Node Study. Axillary lymph node dissection (ALND) was performed in all cases with macrometastases, micrometastases and isolated tumour cells (ITC). RESULTS: The SLN was found in 173/174 patients and a metastatic foci was found in 50 patients including 28/50 with macrometastases, 16/50 with micrometastases and 6/50 with ITC. IHC detected 3/16 of the micrometastases and 4/6 of ITC. Stage migration from N0 to N1mi was encountered in 3/132 patients by use of IHC. Non-SLN metastases were noted in 15/28 of patients with macrometastases and in 3/16 of patients with micrometastases, whereas no patient with ITC had additional metastases (p=0.007). CONCLUSION: The prospective use of IHC and serial sectioning for histopathological diagnosis of SLNs increased the detection rate of N1mi and ITC, but only 3/132 patients were stage-migrated by use of IHC. Patients with ITC did not have any risk of non-SLN metastases, supporting that ALND can safely be omitted in this group of patients.

Adult↗

Insulin-like growth factor I: a predictor of long-term glucose abnormalities in patients with acute myocardial infarction.

AIMS/HYPOTHESIS: Low levels of IGF-I are associated with increased risk of cardiovascular disease and type 2 diabetes. The aim of this study was to investigate the IGF-I system in patients with acute myocardial infarction (AMI) without previously known diabetes. MATERIALS AND METHODS: One hundred and sixty-eight AMI patients were classified before hospital discharge by means of an OGTT as having NGT, IGT or newly detected type 2 diabetes. Age- and sex-matched subjects from the background population (n=185) served as the control group. The associations between fasting levels of IGF-I and IGF binding proteins 1 and 3 (IGFBP-1, IGFBP-3) and glucose metabolism during a follow-up period of 12 months were studied. RESULTS: At hospital discharge, age-adjusted IGF-I (IGF-I SD) was significantly lower in patients with abnormal glucose tolerance (AGT=IGT or type 2 diabetes) compared with patients with NGT (p=0.014) and control subjects (p<0.001). IGF-I was strongly correlated with IGFBP-3 (r=0.730, p<0.001), which was significantly lower in patients with AGT compared with patients with NGT (p=0.009) and control subjects (p<0.001). Fasting levels of IGFBP-1 did not differ significantly between patients with NGT and AGT or between patients and control subjects. In a multiple logistic regression analysis in patients, IGF-I at hospital discharge was a significant predictor of AGT at discharge and after 12 months (adjusted odds ratio 0.29, p=0.022, and adjusted odds ratio 0.29, p=0.034, respectively). CONCLUSIONS/INTERPRETATION: Low levels of IGF-I may be a useful predictor of abnormal glucose metabolism in patients with AMI.

Aged↗

Oral glucose tolerance test is needed for appropriate classification of glucose regulation in patients with coronary artery disease: a report from the Euro Heart Survey on Diabetes and the Heart.

BACKGROUND: Patients with coronary artery disease (CAD) and abnormal glucose regulation (AGR) are at high risk for subsequent cardiovascular events, underlining the importance of accurate glucometabolic assessment in clinical practice. OBJECTIVE: To investigate different methods to identify glucose disturbances among patients with acute and stable coronary heart disease. METHODS: Consecutive patients referred to cardiologists were prospectively enrolled at 110 centres in 25 countries (n = 4961). Fasting plasma glucose (FPG) and glycaemia 2 h after a 75-g glucose load were requested in patients without known glucose abnormalities (n = 3362). Glucose metabolism was classified according to the World Health Organization and American Diabetes Association (ADA; 1997, 2004) criteria as normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes. RESULTS: Data on FPG and 2-h post-load glycaemia were available for 1867 patients, of whom 870 (47%) had normal glucose regulation, 87 (5%) had IFG, 591 (32%) had IGT and 319 (17%) had diabetes. If classification had been based on the ADA criterion from 1997, the proportion of misclassified (underdiagnosed) patients would have been 39%. The ADA 2004 criterion would have overdiagnosed 8% and underdiagnosed 33% of the patients, resulting in a total misclassification rate of 41%. For ethical concerns and practical reasons, oral glucose tolerance test (OGTT) was not conducted in 1495 of eligible patients. These patients were more often women, had higher age and waist circumference, and were therefore more likely to have AGR than those who were included. A model based on easily available clinical and laboratory variables, including FPG, high-density lipoprotein cholesterol, age and the logarithm of glycated haemoglobin A1c, misclassified 44% of the patients, of whom 18% were overdiagnosed and 26% were underdiagnosed. CONCLUSION: An OGTT is still the most appropriate method for the clinical assessment of glucometabolic status in patients with coronary heart disease.

Aged↗

Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes: a report from the GAMI study.

AIMS/HYPOTHESIS: Patients with acute myocardial infarction (AMI) but without previously known type 2 diabetes have a high prevalence of undiagnosed IGT and type 2 diabetes. Such perturbations have dismal prognostic implications. The aim of this study was to characterise AMI patients in terms of insulin resistance and beta cell function. METHODS: A total of 168 consecutive AMI patients were classified by means of an OGTT before hospital discharge as having NGT, IGT or type 2 diabetes. The homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Beta cell responsiveness was quantified as insulinogenic index (IGI) at 30 min (DeltaI(30)/DeltaG(30)). RESULTS: According to the HOMA-IR, patients with type 2 diabetes were more insulin resistant than those with IGT or NGT (p=0.003). Beta cell responsiveness deteriorated with decreasing glucose tolerance as measured by the IGI (median [quartile 1, quartile 3] in pmol/mmol: NGT, 70.1 [42.7, 101.4]; IGT, 48.7 [34.7, 86.8], type 2 diabetes, 38.1 [25.7, 61.6]; p<0.001). The IGI was significantly related to admission capillary blood glucose (r=-0.218, p=0.010) and to the area under the curve for glucose (r=-0.475, p<0.001). CONCLUSIONS/INTERPRETATION: Glucose abnormalities are very common in patients with AMI but without previously known type 2 diabetes. To a significant extent, this seems to be related to impaired beta cell function and implies that dysglycaemia immediately after an infarction is not a stress epiphenomenon but reflects stable disturbances of glucose regulation preceding the AMI. Early beta cell dysfunction may have important pathophysiological implications and may serve as a future target for treatment strategies.

Case-Control Studies↗

Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity.

AIMS: Patients with diabetes have an unfavourable prognosis after an acute myocardial infarction. In the first DIGAMI study, an insulin-based glucose management improved survival. In DIGAMI 2, three treatment strategies were compared: group 1, acute insulin-glucose infusion followed by insulin-based long-term glucose control; group 2, insulin-glucose infusion followed by standard glucose control; and group 3, routine metabolic management according to local practice. METHODS AND RESULTS: DIGAMI 2 recruited 1253 patients (mean age 68 years; 67% males) with type 2 diabetes and suspected acute myocardial infarction randomly assigned to groups 1 (n=474), 2 (n=473), and 3 (n=306). The primary endpoint was all-cause mortality between groups 1 and 2, and a difference was hypothesized as the primary objective. The secondary objective was to compare total mortality between groups 2 and 3, whereas morbidity differences served as tertiary objectives. The median study duration was 2.1 (interquartile range 1.03-3.00) years. At randomization, HbA1c was 7.2, 7.3, and 7.3% in groups 1, 2, and 3, respectively, whereas blood glucose was 12.8, 12.5, and 12.9 mmol/L, respectively. Blood glucose was significantly reduced after 24 h in all groups, more in groups 1 and 2 (9.1 and 9.1 mmol/L) receiving insulin-glucose infusion than in group 3 (10.0 mmol/L). Long-term glucose-lowering treatment differed between groups with multidose insulin (> or =3 doses/day) given to 15 and 13% of patients in groups 2 and 3, respectively compared with 42% in group 1 at hospital discharge. By the end of follow-up, HbA1c did not differ significantly among groups 1-3 ( approximately 6.8%). The corresponding values for fasting blood glucose were 8.0, 8.3, and 8.6 mmol/L. Hence, the target fasting blood glucose for patients in group 1 of 5-7 mmol/L was never reached. The study mortality (groups 1-3 combined) was 18.4%. Mortality between groups 1 (23.4%) and 2 (22.6%; primary endpoint) did not differ significantly (HR 1.03; 95% CI 0.79-1.34; P=0.831), nor did mortality between groups 2 (22.6%) and 3 (19.3%; secondary endpoint) (HR 1.23; CI 0.89-1.69; P=0.203). There were no significant differences in morbidity expressed as non-fatal reinfarctions and strokes among the three groups. CONCLUSION: DIGAMI 2 did not support the fact that an acutely introduced, long-term insulin treatment improves survival in type 2 diabetic patients following myocardial infarction when compared with a conventional management at similar levels of glucose control or that insulin-based treatment lowers the number of non-fatal myocardial reinfarctions and strokes. However, an epidemiological analysis confirms that the glucose level is a strong, independent predictor of long-term mortality in this patient category, underlining that glucose control seems to be an important part of their management.

Aged↗

Pathology parameters and adjuvant tamoxifen response in a randomised premenopausal breast cancer trial.

BACKGROUND: Subgroups of breast cancer that have an impaired response to endocrine treatment, despite hormone receptor positivity, are still poorly defined. Breast cancer can be subdivided according to standard pathological parameters including histological type, grade, and assessment of proliferation. These parameters are the net result of combinations of genetic alterations effecting tumour behaviour and could potentially reflect subtypes that respond differently to endocrine treatment. AIMS: To investigate the usefulness of these parameters as predictors of the response to tamoxifen in premenopausal women with breast cancer. MATERIALS/METHODS: Clinically established pathological parameters were assessed and related to the tamoxifen response in 500 available tumour specimens from 564 premenopausal patients with breast cancer randomised to either two years of tamoxifen or no treatment with 14 years of follow up. Proliferation was further evaluated by immunohistochemical Ki-67 expression. RESULTS: Oestrogen receptor positive ductal carcinomas responded as expected to tamoxifen, whereas the difference in recurrence free survival between control and tamoxifen treated patients was less apparent in the relatively few lobular carcinomas. For histological grade, there was no obvious difference in treatment response between the groups. The relation between proliferation and tamoxifen response seemed to be more complex, with a clear response in tumours with high and low proliferation, whereas tumours with intermediate proliferation defined by Ki-67 responded more poorly. CONCLUSIONS: Clinically established pathology parameters seem to mirror the endocrine treatment response and could potentially be valuable in future treatment decisions for patients with breast cancer.

Adult↗

Cyclin D1 overexpression is a negative predictive factor for tamoxifen response in postmenopausal breast cancer patients.

Antioestrogen treatment by tamoxifen is a well-established adjuvant therapy for oestrogen receptor-alpha (ERalpha) positive breast cancer. Despite ERalpha expression some tumours do not respond to tamoxifen and we therefore delineated the potential link between the cell cycle regulator and ERalpha co-factor, cyclin D1, and tamoxifen response in a material of 167 postmenopausal breast cancers arranged in a tissue array. The patients had been randomised to 2 years of tamoxifen treatment or no treatment and the median follow-up time was 18 years. Interestingly in the 55 strongly ERalpha positive samples with moderate or low cyclin D1 levels, patients responded to tamoxifen treatment whereas the 46 patients with highly ERalpha positive and cyclin D1 overexpressing tumours did not show any difference in survival between tamoxifen and no treatment. Survival in untreated patients with cyclin D1 high tumours was slightly better than for patients with cyclin D1 low/moderate tumours. However, there was a clearly increased risk of death in the cyclin D1 high group compared to an age-matched control population. Our results suggest that cyclin D1 overexpression predicts for tamoxifen treatment resistance in breast cancer, which is line with recent experimental data using breast cancer cell lines and overexpression systems.

Aged↗

Newly detected abnormal glucose tolerance: an important predictor of long-term outcome after myocardial infarction.

AIMS: Recent data revealed that patients with myocardial infarction (MI) have a high prevalence of previously unknown diabetes mellitus (DM) and impaired glucose tolerance (IGT). The added prognostic importance of this finding has not been prospectively explored. To investigate whether a newly detected abnormal glucose tolerance (IGT or DM) assessed early after an MI, is related to long-term prognosis. METHODS AND RESULTS: Patients (n=168; age 63.5+/-9.3 years) with MI, no previous DM and admission blood glucose <11.0 mmol/l were followed for major cardiovascular events defined as the composite of cardiovascular death, non-fatal MI, non-fatal stroke or severe heart failure (HF). According to an oral glucose tolerance test (OGTT) before hospital discharge, 55 patients had normal and 113 abnormal glucose tolerance (GT). During the follow-up of median 34 months there were eight cardiovascular deaths, 15 patients had a recurrent MI, six had a stroke and ten severe HF. All patients who died from cardiovascular causes had abnormal GT. The composite cardiovascular event occurred in 31 (18%) patients. The probability of remaining free from cardiovascular events was significantly higher in patients with normal than abnormal GT (p=0.002). Together with previous MI, abnormal GT was the strongest predictor of future cardiovascular events (hazard ratio 4.18; CI 1.26-13.84; p=0.019). CONCLUSIONS: Abnormal glucose tolerance is a strong risk factor for future cardiovascular events after myocardial infarction. Since it is common and possible to detect even during the hospital phase it may be a target for novel secondary preventive efforts.

Aged↗

Abnormal glucose tolerance--a common risk factor in patients with acute myocardial infarction in comparison with population-based controls.

BACKGROUND: A high prevalence of newly detected diabetes and impaired glucose tolerance (abnormal glucose tolerance) was recently reported in patients with acute myocardial infarction. It is important to verify whether this finding is specific for the patients or attributable to the population, from which they were recruited. OBJECTIVE: To verify whether abnormal glucose tolerance is more prevalent in patients than in controls chosen from the same population and to compare metabolic characteristics between the two groups. DESIGN AND SUBJECTS: The metabolic state was assessed in patients (n = 181) admitted with acute myocardial infarction and no history of diabetes before discharge and after 3 months. Sex- and age-matched controls (n = 185) without previously known diabetes or cardiovascular disease except hypertension were recruited from the general population. MAIN OUTCOME MEASURES: Oral glucose tolerance test, glucosylated haemoglobin A1c (HbA1c), insulin, proinsulin, lipid profile, fibrinolytic function and inflammatory markers. RESULTS: Abnormal glucose tolerance was more common (number/all classified) in patients at discharge 113/168 (67%) and after 3 months 95/145 (66%) than in controls 65/185 (35%) (P < 0.001). Dyslipidaemia (70% vs. 29%; P < 0.001) and previously treated hypertension (32% vs. 18%; P = 0.028) were more frequent amongst patients whilst obesity (18% vs. 24%) did not differ significantly. Blood glucose, HbA1c, proinsulin, proinsulin/insulin ratio, triglycerides, insulin resistance (by HOMA) and fibrinogen were consistently higher in patients than controls (P < 0.01). CONCLUSIONS: Abnormal glucose tolerance was almost twice as common amongst patients with acute myocardial infarction as in matched controls. Impaired glycaemic control accompanied by insulin resistance, dyslipidaemia, hypertension, together with increased plasma fibrinogen and proinsulin levels were main features characterizing patients.

Acute Disease↗

Adhesion, apoptosis and cytokine release of human mononuclear cells cultured on degradable poly(urethane urea), polystyrene and titanium in vitro.

Early interactions between materials and mononuclear cells may influence the viability and secretory response of the cells. Such effects may in turn influence the subsequent inflammatory and repair phases around the materials. In the present study, it was examined if mononuclear cells cultured in vitro either unstimulated or stimulated with lipopolysaccharide (LPS) (10ng/ml) revealed differences regarding cell viability and apoptosis. A major interest was to study the influence of different material properties on the parameters of the inflammatory response upon cell adhesion to materials with widely different surface chemical properties but similar surface topography: degradable poly(urethane urea) (PUUR), cell culture treated polystyrene (PS) surfaces, and commercially pure (c.p.) titanium (Ti). Finally, the secretion of the proinflammatory tumor necrosis factor-a (TNF-alpha) and the downregulating interleukin-10 (IL-10) cytokines was examined in the supernatants from 24h mononuclear cell cultures. No differences in cell viability as measured by lactate dehydrogenas (LDH) were observed between the three materials. The number of material-surface adherent cells was higher on PUUR than the more hydrophilic PS and Ti as judged by quantification of material surface-associated DNA, light microscopic morphological examination of DAPI-stained cells and SEM. LPS increased the number of adherent cells, irrespective of the type of material. The lowest number of apoptotic (annexin-V) and necrotic (propidium iodide) mononuclear cells was detected on PUUR. LPS decreased the number of both apoptotic and necrotic cells, irrespective of material. Low TNF-alpha levels were detected in unstimulated conditions, irrespective of material types. A significantly lower amount of TNF-alpha was found with unstimulated cells on PUUR than on Ti. A significantly higher IL-10 level was detected in unstimulated Ti cultures compared with PUUR and PS. Secretion of IL-10 was predominantly stimulated by LPS on PUUR and Ti. The data indicate that material-related differences are expressed in differences in cell adherence, apoptosis and cytokine secretion. Further, degradable PUUR has equal or less cell-activating properties than Ti and PS under in vitro conditions.

Absorbable Implants↗

Mode of death in heart failure: findings from the ATLAS trial.

OBJECTIVE: To investigate markers that predict modes of death in patients with chronic heart failure. DESIGN: Randomised, double blind, three period, comparative, parallel group study (ATLAS, assessment of treatment with lisinopril and survival). PATIENTS: 3164 patients with mild, moderate, or severe chronic heart failure (New York Heart Association functional class II-IV). INTERVENTIONS: High dose (32.5 or 35 mg) or low dose (2.5 or 5 mg) lisinopril once daily for a median of 46 months. MAIN OUTCOME MEASURES: All cause mortality, cardiovascular mortality, sudden death, and chronic heart failure death related to prognostic factors using competing risks analysis. Mode of death was classified by trialists and by an independent end point committee. RESULTS: Age, male sex, pre-existing ischaemic heart disease, increasing heart rate, creatinine concentration, and certain drugs taken at randomisation were markers of increased risk of all cause mortality and cardiovascular death. There were risk markers for sudden death that were different from the risk markers for death from chronic heart failure. Low systolic blood pressure at baseline, raised creatinine, reduced serum sodium or haemoglobin, and increased heart rate were associated with chronic heart failure death. Use of beta blockers or antiarrhythmic agents (mainly amiodarone) was associated with a reduced risk of sudden death, whereas long acting nitrates and previous use of angiotensin converting enzyme inhibitors were markers for increased risk. CONCLUSIONS: The use of competing risks analysis on the data from the ATLAS study has identified variables associated with certain modes of death in heart failure patients. This approach to analysing outcomes may make it possible to predict which patients might benefit most from particular therapeutic interventions.

Aged↗

Significant predictors of poor prognosis in women aged </=65 years hospitalized for an acute coronary event.

OBJECTIVES: The aim of this study was to evaluate the importance of different clinical parameters predicting long-term cardiac prognosis in younger women with an acute coronary event. DESIGN: The Stockholm Female Coronary Risk Study is a follow-up study in women </=65 years. SETTING: Patients were included between 1991 and 1994 from all 10 coronary care or intensive care units in the greater Stockholm area. SUBJECTS: A total of 335 consecutive female patients hospitalized for an acute coronary event. MAIN OUTCOME MEASURES: Cardiac death and nonfatal myocardial infarction (AMI). RESULTS: During the follow-up period of 5 years there were 26 (8%) all cause deaths and 39 (12%) recurrent cardiac events. In the group that participated in the complete study, the following age adjusted parameters were found as strong predictors of adverse outcome: AMI as index event [Hazard Ratio (HR) 9.13, 95% CI 3.09-26.99], diabetes mellitus (HR 4.13, 95% CI 1.68-10.17), left ventricular dysfunction (HR 3.94, 95% CI 1.52-10.17), serum HDL cholesterol <1.0 mmol L-1 (HR 4.01, 95% CI 1.62-6.12), and serum triglycerides >2.0 mmol L-1 (HR 2.46, 95% CI 1.06-5.54). AMI as index event and diabetes mellitus were the most significant predictors in a multivariate statistical model. Diabetes mellitus was the strongest predictor when the analysis was repeated in the total patient cohort, integrating patients that did not participate in the extended investigations. CONCLUSION: Women aged </=65-year-old hospitalized for an acute coronary event has a low rate of cardiac events during the following 5-year period. Easily obtained clinical variables such as diabetes mellitus predict adverse prognosis and implicates a need for a more active diagnostic and treatment strategy.

Adult↗

Continuous haemodynamic monitoring during withdrawal of diuretics in patients with congestive heart failure.

AIMS: Right heart pressure parameters can be recorded continuously with the help of an implanted haemodynamic monitor. The aim of this study was to investigate the usefulness of the device in adjusting diuretic medication in patients with chronic congestive heart failure, and to evaluate the response of right ventricular pressure to increased volume load induced by diuretic withdrawal. METHODS AND RESULTS: Four patients with stable congestive heart failure were implanted with an implantable haemodynamic monitor. Furosemide, the only diuretic used, was reduced by 50% the first week, withdrawn completely for the second week and then reinstituted in the initial dose. Right ventricular systolic and diastolic pressure, pulse pressure, dP/dt, estimated diastolic pulmonary artery pressure and heart rate were sampled continuously. Patients were evaluated by body weight, NYHA class, serum creatinine, serum brain natriuretic peptide, the 6 min walk test, quality of life and echocardiography on days 0, 7, 14 and 21. We observed significant changes in right ventricular pressure parameters in parallel with clinical signs and symptoms of worsening heart failure, such as increased body weight, a shorter walking distance and impaired quality of life. Moreover elevated levels of brain natriuretic peptide and lower creatinine levels were observed. CONCLUSION: Haemodynamic changes due to increased volume load can be detected with an implantable haemodynamic monitor. Such data provide useful information for tailoring an optimal diuretic dose in patients with congestive heart failure.

Aged↗

Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival.

BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. METHODS: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.

Aged↗

Management of atrial fibrillation: discrepancy between guideline recommendations and actual practice exposes patients to risk for complications.

AIMS: To assess compliance to guidelines in the management of patients with atrial fibrillation. METHODS AND RESULTS: A total of 728 questionnaires were mailed to physicians with the intention of studying 'theoretical' compliance to practice guidelines. A retrospective evaluation of 200 records from consecutive patients hospitalized with atrial fibrillation was performed in order to verify 'actual' compliance to guidelines. The response rate to the questionnaires was 68%. More than 94% of the physicians stated that patients with risk factors for thromboembolic complications and chronic atrial fibrillation should receive long-term warfarin treatment. Of evaluated records, 108 patients were in chronic atrial fibrillation with at least one risk factor for stroke, and with no known contraindication to warfarin. In this group, only 40% received warfarin. Moreover, several other discrepancies were detected as regards the use of antiarrhythmic therapy. CONCLUSION: This study reveals a clear discrepancy between recommendations in guidelines and actual practice in patients with atrial fibrillation. The most important finding was a significant under use of thromboembolic prophylaxis in patients at high risk for such events. Implementation and the study of adherence to management guidelines on atrial fibrillation need to be carefully reviewed by surveys of actual clinical practice in order to establish reasonable therapeutic quality.

Adult↗

Continuous ambulatory monitoring of absolute right ventricular pressure and mixed venous oxygen saturation in patients with heart failure using an implantable haemodynamic monitor: results of a 1 year multicentre feasibility study.

BACKGROUND: Implantable sensors that monitor haemodynamics over time may be useful in patients with heart failure. This multicentre study assessed the feasibility of a system that has one sensor measuring absolute pressure and another measuring mixed venous oxygen saturation (SvO(2)). Both sensors were mounted on leads that were implanted in the right ventricle. METHODS: Twenty-one patients with heart failure (NYHA II-III) were included. Comparisons were made to right heart catheterizations at implant and at 2, 6 and 12 months thereafter. Patients underwent several haemodynamic provocations during the catheterizations. RESULTS: Overall, among functioning sensors, the IHM-1 values were highly correlated with reference values for all time points during all provocations, demonstrating high reproducibility and stability (r(2)=0.91, 0.79 and 0.78 for systolic, right ventricular diastolic and SvO(2), respectively). Although IHM-1 underestimated reference pressure values by 4.5 mmHg and SvO(2)by 1.6%, this difference was consistent across provocation and stable over 12 months of follow-up. Twelve of the 21 oxygen sensors failed to function and two pressure sensors had component failures. Preliminary analysis of long-term data revealed haemodynamic patterns that may be key indicators for therapeutic interventions. CONCLUSION: This multicentre feasibility study demonstrated the accuracy and stability of sensors implanted in the right ventricle. The IHM-1, using right ventricular pressures and SvO(2), with improved performance, might be useful in the study of pathophysiological mechanisms and treatment interventions in heart failure.

Adult↗