Evidence against heterozygous coagulation factor V 1691 G-->A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction.

The aim of our study was to determine the prevalence of the factor V mutation (position 1691 G-->A) in patients with angiographically diagnosed coronary artery disease and myocardial infarction and, as a control, in blood donors. This mutation has already been proved to be the main genetic risk factor for venous thrombosis. In order to detect this mutation in exon 10 of the factor V gene we established a microtiter plate based hybridization assay for the specific detection of wild-type and mutant sequences in factor V gene segments, obtained after amplification by polymerase chain reaction. This test enables us to screen a large number of samples. The mutation was detected in 29 of 317 coronary artery disease (CAD) patients (9.1%) and 18 of 190 blood donors (9.5%) investigated. The mean activated protein C resistance ratios were 3.18 and 3.11, with nearly identical distribution. No increased prevalence of the factor V mutation was found in the CAD group. In 10 of 29 CAD patients (35%) with the factor V 1691 G-->A mutation and in 124 of 288 CAD patients without the mutation (43%) there was a history of myocardial infarction. From our data we conclude that there is no increased risk of developing coronary atheroma or consecutive myocardial infarction resulting from the factor V mutation with protein C resistance.

Results of heart transplantation in patients with preexisting malignancies.

Twenty patients with end-stage heart failure and preexisting malignancies underwent heart transplantation at a single center, with a neoplasm-free interval before the procedure of 0 to 240 months. Twelve patients were long-term survivors (2 to 72 months); there were 2 early and 6 late deaths, thus justifying heart transplantation in patients with preexisting malignancies in individual cases.

Tuberculosis in heart transplant recipients.

STUDY OBJECTIVES: To clarify the prevalence and factors associated with tuberculosis, as well as patient survival in heart transplant recipients. DESIGN: A retrospective review of case records of all heart transplant recipients from March 1989 to February 1996 during a 7-year period. SETTING AND PATIENTS: During the period reviewed, 727 orthotopic heart transplantations were performed in 716 patients at the Heart Center Northrhine-Westphalia, Germany. RESULTS: Tuberculosis was proved in seven (1%) patients (four men/three women; age, 33 to 71 years; two miliary lesions, three pulmonary lesions, and two urogenital lesions). None of them had primary history of tuberculosis. Tuberculin skin tests were not performed before transplantation because there were no lesions indicating primary infection of turberculosis. The immunosuppressive regimen was based on double-drug (cyclosporine + azathioprine) therapy. Immunosuppression had been intensified by methylprednisolone pulses at least three times in those seven patients, and prednisone had been used orally in six of seven patients. Tuberculosis developed from 2.5 to 41 months after transplantation. Tuberculosis was found by routine examinations in four of seven patients. Diagnoses were made with both direct microscopy and cultures in six patients, and by histologic study in one. Treatment consisted of isoniazid, rifampicin, ethambutol, and pyrazinamide. Two patients with miliary lesions were treated with four drugs, and the others were treated with three drugs. Isoniazid was used in all patients. Rifampicin, which decreases cyclosporine serum levels, was not used from the beginning in one patient and treatment with it was stopped halfway in another patient because low cyclosporine level had induced rejection. Six of the seven patients are doing well while receiving antituberculous therapy. One patient died with miliary tuberculosis as a cause of death. CONCLUSIONS: The prevalence of tuberculosis in heart transplant recipients was higher than that in the general population. We recommend that a high degree of clinical suspicion is maintained for tuberculosis in heart transplant recipients with meticulous follow-up, and that the treatment of tuberculosis has to be with meticulous care, especially during the use of rifampicin.

Predictors of unsuccessful outcome after percutaneous mitral valvulotomy including a new echocardiographic scoring system.

BACKGROUND AND AIMS OF THE STUDY: Percutaneous mitral valvulotomy has been shown to be an accept able alternative to surgery as treatment for selected patients with severe mitral stenosis. Uncertainty still exists regarding predictors of unsuccessful outcome. MATERIALS AND METHODS: 308 patients with severe mitral stenosis underwent Inoue single balloon valvulotomy over a 48-month period and were followed up for a mean of 14.5 +/- 16.8 months (range one to 64 months). Two hundred and sixty-seven (Group I) improved clinically and remained stable throughout the follow up, while subsequent surgery was required in 41 (Group II) after 38.2 +/- 143.5 days (range one to 1,212). Clinical and echocardiographic parameters of the two groups were compared to find significant predictors of an unsuccessful outcome. RESULTS: Significant differences between the groups were observed for NYHA class (2.7 +/- 0.6 vs. 2.9 +/- 0.6, p < 0.05), mitral valve area (1.0 +/- 0.3 vs. 0.9 +/- 0.2 cm2, p < 0.01), left atrial end-systolic dimension by echo (51.3 +/- 8.0 vs. 55.4 +/- 10.2 mm, p < 0.01) and an echocardiographic scoring system including grading for eccentricity of the mitral orifice and distribution of commissural calcification (7.5 +/- 2.0 for Group I and 8.7 +/- 2.0 for Group II, p < 0.001). CONCLUSIONS: Mitral valves that are more likely to have an unsuccessful outcome can be identified by hemodynamic, clinical and echocardiographic criteria, including grading for eccentricity of the mitral orifice and distribution of commissural calcification.

Validation of the Omron F3 blood pressure measuring device for use in the finger through simultaneous invasive comparative measurements according to the German Institute for Validation (DIN) 58130 protocol.

OBJECTIVES AND DESIGN: Simultaneous invasive comparative measurements in order to validate the blood pressure measuring device Omron F3 for use in the finger, in accordance with the German Institute for Validation (DIN) 58130 protocol. METHODS: A total of five consecutive simultaneous blood pressure comparative measurements were carried out in each of 15 patients (n = 75). Blood pressure was measured in the left index finger using the blood pressure measuring device Omron F3, and at the same time invasively using a pigtail catheter situated in the aortic arch. The measuring arrangements, validation of the unit of invasive measurement and evaluation were all carried out in accordance with the DIN 58130 protocol. RESULTS: The blood pressure measuring device Omron F3 for use in the finger fulfils the criteria of the European Standard prEn 1060-3. Systolic blood pressure decreased by 2.9+/- 6.6 mmHg and diastolic blood pressure decreased by 2.6+/- 5.9 mmHg. CONCLUSION: The blood pressure measuring device Omron F3 measures blood pressure reliably and accurately if used correctly in appropriate patients. Before using the device for the first time, comparative blood pressure measurements in the upper arm, using the standard auscultatory blood pressure measurement technique according to Riva-Rocci and Korotkoff, should be carried out, in order to check the accuracy of measurement.

Correlation between R-wave amplitude and left ventricular volume at rest and with exercise.

In 52 patients with exercise angiography (12 normals, 31 with coronary heart disease, 9 with congestive cardiomyopathy) exercise ECGs were examined for R-wave changes. An increasing R-wave amplitude was found an insensitive sign of ischemia in patients with coronary heart disease (sensitivity 29%, specificity 81%). Sensitivity and specificity of the observed ST depression in this study were 83% and 71%, respectively, as reported by others. There was no positive correlation between the changes in the R-wave amplitude and left ventricular end-diastolic volume during exercise, thus there was no proof of the existence of the so-called Brody effect in humans.

Influence of heart rate on systolic time intervals: effects of atrial pacing versus dynamic exercise.

The effects of atrial pacing and dynamic exercise in the supine position on systolic time intervals (STI) were compared in 10 normals. In another group of 13 normals, the effect of exercise alone on STI was tested. A linear shortening of electromechanical systole (QS2) and left ventricular ejection time (LVET) with increasing heart rate was demonstrated with right atrial pacing and dynamic exercise in the frequency range between 60 and 140 beats/min. However, the shortening of LVET was significantly less (p less than 0.01) with exercise compared to pacing. This is explained by an increase in left ventricular stroke volume with exercise. The preejection period (PEP) was significantly (p less than 0.001) shortened with exercise, but there was no change with atrial pacing. Thus, changes in heart rate (HR) alone, without changes in the dynamic state of the heart, did not influence PEP. It is suggested that PEP at rest should not be corrected for heart rate. The supine exercise regression equations for correction of heart rate for LVET and PEP differ from both the resting and the upright exercise regression equations. With exercise a frequency correction of STI using regression equations should be abandoned. Instead, uncorrected STI at standard heart rates (e.g., 100, 110, and 130 beats/min) should be taken for comparison. Heart rate standardization should be employed using the formula: Formula (See Text).

Reconstructing medical problem solving competence: MACCORD.

The building of medical knowledge-based systems involves the reconstruction of methodological principles and structures within the various subdomains of medicine. ACCORD is a general methodology of knowledge-based systems, and MACCORD its application to medicine. MACCORD represents the problem solving behavior of the medical expert in terms of various types of medical reasoning and at various levels of abstraction. With MACCORD the epistemic and cognitive processes in clinical medicine can be described in formal terminology, covering the entire diversity of medical reasoning. MACCORD is close enough to formalization to make a significant contribution to the fields of medical knowledge acquisition, medical didactics and the analysis and application of medical problem solving methods.

Pathomorphological characteristics of resected mitral valves after unsuccessful valvuloplasty.

OBJECTIVE: Percutaneous mitral valvuloplasty has been shown to be an acceptable alternative to surgery as treatment for selected patients with severe mitral stenosis. We examined hemodynamic, echocardiographic, and pathomorphologic findings in a series of 308 patients undergoing balloon valvuloplasty, 41 of whom underwent subsequent surgery, in search of possible predictors of an unsuccessful outcome. INTERVENTION AND RESULTS: Patients with severe mitral stenosis underwent Inoue single ballon valvuloplasty over a 48-month period and had follow-up for a mean of 14.5+/-16.8 months (range 1 to 64 months). Of the 308 patients, 267 (Group I) were clinically improved and stable throughout follow-up, while subsequent surgery was required in 41 (Group II) after 38.2+/-143.5 days (range 1 to 1212). Significant differences between the groups were observed for NYHA class (2.7+/-0.6 vs 2.9+/-0.6, p<0.05), mitral valve area (1.0+/-0.3 vs 0.9+/-0.2 cm2, p<0.01) and left atrial endsystolic dimension by echo (51.3+/-8.0 vs 55.4+/-10.2 mm, p<0.01). Two of the 41 Group II patients underwent surgery for left to right shunting, 1 for tamponade and 2 were lost to follow-up. The excised mitral valves of the remaining 36 patients all showed calcification and/or fibrosis: 9 homogenous, 5 non-homogenous; 19 were classified as having a funnel-shaped deformity, and 3 did not fit into a discrete category. Among the funnel-shaped valves, 13 had a tear versus 6 where dilation was primarily accomplished by stretching. Only one of 9 valves with homogenous calcification was torn, whereas a tear was noted in 3 of the 5 with non-homogenous calcification. CONCLUSION: Funnel-shaped valves and those with non-homogenous distribution of calcification and/or fibrosis appear to be least suitable for balloon valvuloplasty.

[Clinical significance of the cardiovascular risk factor fibrinogen in secondary prevention]. / Klinische Bedeutung des kardiovaskulären Risikofaktors Fibrinogen in der Sekundärprävention.

Seven prospective, epidemiological studies indicate plasma fibrinogen levels (over 300-350 mg/dl) as an important, independent cardiovascular risk factor for subsequent myocardial infarction and stroke. Furthermore, several clinical studies revealed an association between fibrinogen and both the angiographic and clinical degree of coronary heart disease. In addition, a significant relation of fibrinogen with the number of occluded coronary vessels was found. The following pathophysiologic mechanism are of particular importance: Fibrinogen is a main determinant of plasma viscosity and red cell aggregation. Both phenomena deteriorate blood fluidity especially in the microcirculation. Fibrinogen plays a central role in platelet aggregation and performs an essential substrate in the coagulation cascade. Thus, high fibrinogen levels may favor a hypercoagulable state resulting in final thrombotic events of cardiovascular disease. Fibrinogen is also involved in atherogenesis by stimulating proliferation and migration of smooth muscle cells. Several determinants of fibrinogen levels are known. Smoking is the strongest one in healthy persons. This clinically important effect is dose related. Consequently, cessation of smoking is a major step to lower fibrinogen and subsequently the individual cardiovascular risk. Reduction of overweight and maintenance of regular physical activity are further nonpharmacologic means. Fibrates decrease fibrinogen about 10-30% on an average. Finally, intermittent low-dose Urokinase for end-stages of coronary artery disease and LDL-apheresis (HELP) represent additional approaches to reduce fibrinogen.

Educating nurses in blood pressure measurement and hypertension control.

Today, self-measurement of blood pressure is seen as the optimal goal in improving the compliance of the hypertensive patient, but it can only be reached by using well trained medical staff. In this, the role of nurses is particularly vital. We administered a questionnaire to 77 nurses and 146 doctors to determine their levels of knowledge concerning blood pressure measurement techniques and pitfalls, and definition of hypertension. The general knowledge of both groups was insufficient. Whereas doctors showed greater medical knowledge, nurses were better at the techniques. Both were equally deficient in defining hypertension. We therefore set up a short course (3h) in blood pressure measurement to evaluate knowledge and provide further training. The course consisted of a pretest, a short training programme and a post-training test. Post-training test results showed an average improvement in defining hypertension from 5% to 85%. We conclude that short-term training courses in blood pressure measurement are needed for nurses and doctors, particularly young doctors. We also need more coverage in the medical press to stimulate interest in this vital topic.