Genetic polymorphisms and heart failure.

Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism. Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system. Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study gene-gene interactions and gene-environment interactions.     

Measuring quality of life in patients with myocardial infarction or stroke: a feasibility study of four questionnaires in The Netherlands.

OBJECTIVE--To test in patients with a history of myocardial infarction or stroke the feasibility of four quality of life measurements--the Nottingham health profile (NHP), the heart patients psychological questionnaire (HPPQ), the sickness impact profile (SIP), and the hospital anxiety and depression scale (HAD). DESIGN--Subjects were tested and retested after an interval of 14 days: questionnaires were self assessed. SUBJECTS--Participants were randomly selected from the Rotterdam stroke data bank (stroke patients; n = 16, mean (SD) age 66.0 (11.0) years and from the population based Rotterdam study (myocardial infarction; n = 20, mean (SD) age 72.7 (7.9) years, controls; n = 17, mean (SD) age 72.8 (7.3) years. MEASUREMENTS AND MAIN RESULTS--Mean (SD) administration times for the NHP, HPPQ, SIP, and HAD were 7.9 (3.5), 10.5 (4.3), 21.0 (9.8), and 5.5 (2.8) minutes respectively. On average, the test-retest reliability was good, with Spearman correlations ranging from 0.31 to 0.95. In spite of the limited size of the study, all instruments were able to show differences between the study groups. For instance, median SIP total scores for myocardial infarction and stroke patients were 12.4 (interquartile range 7.0-19.1) and 11.4 (5.9-15.4) respectively, compared with 7.7 (3.7-11.3) in the control group (p values of 0.04 and 0.14 respectively). CONCLUSIONS--This study suggests that use of the four instruments tested may be feasible and reliable for assessing aspects of quality of life in patients with a history of a myocardial infarction or stroke.     

Measuring maternal mortality: An overview of opportunities and options for developing countries

Background  

There is currently an unprecedented expressed need and demand for estimates of maternal mortality in developing countries. This has been stimulated in part by the creation of a Millennium Development Goal that will be judged partly on the basis of reductions in maternal mortality by 2015.     

Leucocyte Migration Test and Hypersensitivity to Glafenin

The leucocyte migration test (LMT) was performed on 20 patients with an intolerance to glafenin--a non-narcotic analgesic drug. LMT was found to be positive in 50% of the subjects with intolerance, a highly significant percentage as compared with the control groups. HSA-glafenin was found to be the most appropriate method for presenting the antigen, but glafenin and its hydroxylated metabolites were only found to induce a migration inhibition in the subjects intolerant to glafenin.     

Classification of heart failure in population based research: An assessment of six heart failure scores

Several scores based on symptoms and signs have been developed to assess the presence of heart failure. The goal of this study was to compare six heart failure scores in non-hospitalised subjects and to determine their usefulness in population based research. The scores were applied to 54 participants of a population based study. All underwent a complete medical examination, including chest X-ray, electrocardiography and Doppler echocardiography. Using all information available, a cardiologist, unaware of the results of the scores, clinically classified participants as having no, possible or definite heart failure. Sensitivity, specificity, predictive values and receiver operating characteristics were calculated, using the cardiologist's assessment as a gold standard. The cardiologist judged definite or possible heart failure to be present in 17 persons. All scores had a high sensitivity for the detection of definite heart failure, whereas the study of men born in 1913 and Walma's score had the highest sensitivity for the combination of possible and definite heart failure. Gheorgiade's and the Boston score had the highest positive predictive values. In conclusion, five of the six scores we studied are broadly similar in the detection of heart failure. The men born in 1913 score relies heavily on the assessment of dyspnea, resulting in a relatively large number of false positives. Although the scores are useful in detecting manifest heart failure, objective measurements of cardiac function appear necessary to reduce the false positive rate and accurately detect early stages of heart failure.     

Implementation of a pre-hospital decision rule in general practice: Triage of patients with suspected myocardial infarction

OBJECTIVE: To improve pre-hospital triage of patients with suspected acutecardiac disease DESIGN: Prospective study SUBJECTS: Patients with symptoms suggestive of acute cardiac pathology,who were seen by a general practitioner, for whom acute admissioninto hospital was requested, and in whom a pre-hospital electrocardiogramwas recorded by the ambulance service METHODS: The study consisted of two phases. In the first phase, a decisionrule was developed based on clinical characteristics and electrocardiographicfindings in 1005 patients with suspected acute cardiac pathology.In the second phase, the decision rule was prospectively validated.Symptoms were recorded by a standardized questionnaire by thegeneral practitioner and a computerized electrocardiogram wasmade by the ambulance nurses at the patient's home. Three electrocardiographicoutcomes were available: ‘normal electrocardiogram’,‘possible myocardial infarction’ or ‘extensivemyocardial infarction’. By use of the predictive model,the general practitioner could decide if hospitalization wasnecessary or not. MAIN OUTCOME MEASUREMENTS: Identification of patients at low (stable angina, atypical chestpain, other pathology) and high (myocardial infarction, unstableangina) probability of acute cardiac pathology. RESULTS: Among 977 patients with a complete pre-hospital evaluation inthe validation phase of the study, the decision rule recommended‘no hospitalization’ in 227 patients (23%). Thegeneral practitioner followed this advice in 44% of these patients.Although seven of them developed a non-Q wave myocardial infarction,no complications occurred in patients not admitted. In addition,the general practitioner did not hospitalize 19 (2%) of 750patients for whom the decision rule recommended admission. Prehospitaltriage by the general practitioner resulted in a 12% (118 of977 patients) reduction of the number of patients admitted tothe Coronary Care Units. CONCLUSIONS: Pre-hospital triage by the general practitioner was facilitatedusing a standardized questionnaire and pre-hospital electrocardiography,and resulted in a reduction in the number of patients admittedto the Coronary Care Unit, and proved to be safe.     

The TNM classification adapted to palliative care]

The staging of tumors according to the "TNM" system was developed by P Denoix between 1943 and 1952. The "TNM" system is based on 3 items of data: the clinical aspect of the tumor "T", the regional lymph nodes "N", and the presence or absence of distant metastases. According to the extent of the local, regional and distant sites the TNM system permits definition of tumor stage. These stages allow comparison of the results from different centers to be made and the establishment of treatment protocols. We have taken the principles of the TNM staging of the UICC and the AJCC staging and applied them to "palliative stages" of cancer patients in an attempt to define the profile of the "palliative care patient", and to exchange the results of treatment between cancer centers.     

Concept of an antiatherosclerotic efficacy of calcium entry blockers

Animal experiments suggest an inhibitory effect of calcium entry blockers on arterial calcinosis and the formation of atherosclerotic plaques. Experiments with isolated tissues suggest various mechanisms for an antiatherosclerotic effect of calcium entry blockers.INTACT, the International Nifedipine Trial on Antiatherosclerotic Therapy, is the first study investigating, with a prospective, placebo-controlled, randomized, double-blind design, the influence of a calcium entry blocker (nifedipine 80 mg/day) on the progression of coronary atherosclerosis in patients with proven coronary artery disease. Study endpoints were changes of established coronary stenoses (diameter reduction 20%), as well as the formation of new stenoses as documented by coronary angiography. Standardized coronary angiograms were taken before and after a treatment period of 3 years. The angiograms were quantitatively analyzed with the computer-assisted edge detection system CHAS. Of the 425 patients included in the study, 282 patients (134 on nifedipine and 148 on placebo) revealed no protocol violations. In the inclusion angiograms of these patients, 893 coronary stenoses were detected which were not significantly influenced in their development by nifedipine. However, 196 entirely new coronary lesions, 185 stenoses and 11 occlusions, were found in the follow-up angiograms. There were 78 lesions in 54 patients (40%) on nifedipine (0.58 new lesions/patient) and 118 lesions in 73 patients (49%; n.s.) on placebo (0.8 new lesions/patient; p = 0.031).