HLA-B27-associated heart disease. Clinicopathologic study of three cases.

The histologic features of the cardiac lesions in HLA-B27-associated heart disease were examined in three cases that illustrate different nuances of the clinical spectrum of this disorder. One of these cases constitutes an important link between the previously established concept of cardiac manifestations in ankylosing spondylitis and Reiter's disease and the recently introduced, wider concept of HLA-B27-associated cardiac manifestations. A correlation between the invasive electrophysiologic results and the autopsy findings is demonstrated in another case.

Ankylosing spondylitis: an important cause of severe disturbances of the cardiac conduction system. Prevalence among 223 pacemaker-treated men.

The cause of severe disturbances of the cardiac conduction system is seldom possible to establish clinically at pacemaker implantation, apart from cases of acute myocardial infarction or digitalis intoxication and in relatively rare cases of inflammatory disorders such as sarcoidosis and systemic sclerosis. Since cardiac manifestations, mainly conduction disturbances, occur in patients with ankylosing spondylitis, the prevalence of this disease was determined using radiologic screening for sacroiliitis in a population of 223 men who had permanently implanted pacemakers. Sacroiliitis was found in 19 men (8.5 percent), 15 of whom fulfilled the diagnostic criteria for ankylosing spondylitis. In six patients, sacroiliitis was asymptomatic and two of the patients were completely free of symptoms other than those originating from their heart manifestations. In seven of the 15 patients with ankylosing spondylitis and in the four patients with sacroiliitis without clinical criteria of ankylosing spondylitis, the diagnosis was previously unknown. Uveitis and aortic regurgitation occurred in five patients each, while peripheral arthritis was twice as common. The prevalence of sacroiliitis and ankylosing spondylitis of 8.5 and 6.7 percent, respectively, differ significantly (p less than 0.01) from the frequencies found in general Caucasian populations of 1 to 2 and 0.1 to 0.5 percent, respectively. HLA B27 was present in more than 80 percent of the patients with sacroiliitis and/or ankylosing spondylitis, compared with 8 to 10 percent in the general population. This strong association is in accordance with previous studies of patients with symptomatic sacroiliitis and/or ankylosing spondylitis. Thus sacroiliitis, diagnosed by x-ray, can be considered a marker for this relatively common rheumatic cause of severe disturbances of the cardiac conduction system.

HLA-B27: an important genetic risk factor for lone aortic regurgitation and severe conduction system abnormalities.

PURPOSE: HLA-B27, an immunogenetic marker that is present in 8 percent of the white population around the world, has been found to be an important risk factor for the development of a group of rheumatic disorders, the seronegative spondyloarthropathies. Our objective was to assess the possible role of HLA-B27 and the associated inflammatory disease process in the development of lone aortic regurgitation. PATIENTS AND METHODS: A group of 91 patients with lone aortic regurgitation were studied by HLA typing and clinical and roentgenologic examination. RESULTS: The HLA-B27-associated inflammatory disease process was found to be the probable underlying cause in 15 to 20 percent of patients with lone aortic regurgitation of different degrees of severity. Furthermore, HLA-B27 was found in 88 percent of the male patients with the combination of aortic regurgitation and severe conduction system abnormalities. CONCLUSION: We suggest that this cardiac syndrome should be regarded as an HLA-B27-associated syndrome, sometimes part of ankylosing spondylitis or Reiter's disease, but just as often presenting without obvious rheumatic disease. The marker is thus an important and widely distributed risk factor not only for the development of rheumatic disease but also for acquired aortic regurgitation and sever conduction system abnormalities.

Atrioventricular block progression in patients with bifascicular block assessed by repeated electrocardiography and a bradycardia-detecting pacemaker.

Syncope may be due to intermittent high-degree atrioventricular (AV) block, but a cause-relation is sometimes difficult to prove. Diagnostic methods with high predictive value proven by instruments for safe and sensitive follow-up are needed. A bradycardia-detecting pacemaker was used in patients with bifascicular block, who had been the subjects of pharmacologic stress testing of the His-Purkinje system. Thirty-seven patients were included, of whom 26 had experienced at least 1 syncopal episode of suspected bradycardia origin, and 11 had previously documented transient high-degree AV block. The electrophysiologic study included injection of disopyramide 2 mg/kg (up to 150 mg) over 5 minutes. A positive test result was defined as spontaneous or pacing-induced His-Purkinje high-degree AV block after drug or a drug-induced HV prolongation of > or = 50%. Patients were followed an average 63 months with repeated electrocardiography and a diagnostic pacemaker (n = 23). Altogether, 24 patients had a significant bradycardia diagnosed by either or both methods. The sensitivity and positive predictive values were: HV interval > or = 70 ms at baseline, 47% and 88%; a positive disopyramide test result, 75% and 80%; and HV interval > or = 70 ms or a positive disopyramide test result, 93% and 74%, respectively. Thus, the diagnostic pacemaker is a safe and sensitive tool for evaluating the information obtained at electrophysiologic study, and pharmacologic stress testing with disopyramide has an informative value in patients with bifascicular block and syncope when results at baseline are inconclusive.

A low-threshold, non-dislocating endocardial electrode.

Threshold curves with large and small surface intracardiac pacemaker electrodes are compared. The 2 msec. impulse threshold with a 47 sq. mm. electrode was 3.6 v. (4.3 mA.) on the fourteenth postoperative day, when it reached its maximum, and 2.8 v. (3.1 mA.) one month after the operation. These values were 45 and 30 per cent lower with a 6 sq. mm. electrode. Thresholds increased by about 20 per cent when the impulse duration was shortened from 2 to 0.5 msec. The small surface electrode consumed about 35 per cent less current than the 47 sq. mm. one. A newly designed large area-small surface electrode with the shape of an open cage, seems to have the advantages of less increase in postoperative thresholds and good attachment to the endocardial wall.

In vivo biosynthesis of thromboxane and prostacyclin during exposure to physiological levels of epinephrine.

The effects of 20-min epinephrine infusion (0.025 and 0.3 nmol/kg/min) on the in vivo synthesis of thromboxane A2 and prostacyclin were studied in ten healthy male volunteers. We assessed the in vivo biosynthesis of thromboxane A2 and prostacyclin by measurement of the urinary metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha, respectively. Epinephrine infusion did not cause any significant changes in the urinary excretion of the two metabolites. Thus, we conclude that physiological levels of epinephrine do not affect the in vivo biosynthesis of thromboxane A2 and prostacyclin.

In vivo production of thromboxane in acute human myocardial infarction: a preliminary study.

Using a specific quantitative method based on gas chromatography-mass spectrometry the urinary excretion of 2,3-dinor-TxB2 was measured in five patients with acute myocardial infarction shortly after the onset of symptoms. The urinary excretion of 2,3-dinor-TxB2 was markedly higher than seen in normals in three of the five patients. This increased excretion of 2,3-dinor-TxB2 during and after the development of myocardial necrosis indicates an involvement of thromboxane A2 in the pathogenesis of at least some cases of acute myocardial infarction.

Activators and inhibitors of coagulation and fibrinolysis in patients with prostatic cancer treated with oestrogen or orchidectomy.

The treatment of prostatic cancer with oestrogen has been reported to be associated with cardiovascular side effects. Twenty patients with recently diagnosed prostatic cancer were randomly allocated to oestrogen therapy or orchidectomy. As compared to healthy age matched controls the patients with prostatic cancer had increased base-line levels of fibrinogen (5.2 +/- 1.9 g/l versus 3.7 +/- 1.0 g/l; p less than 0.002) and factor VIII:C (166 +/- 62% versus 110 +/- 29%; p less than 0.001). During oestrogen therapy factor VII increased from 99 +/- 22% to 150 +/- 47% (p less than 0.001), while the antithrombin III level fell from 93 +/- 10% to 81 +/- 13% (p less than 0.001). Both these changes are in the direction of a hypercoaguable state. Concomitantly plasminogen increased from 113 +/- 14% to 142 +/- 18% (p less than 0.001), urokinase inhibiting activity fell from 105 +/- 10% to 90 +/- 9% (p less than 0.001) and C1-esterase inhibitor fell from 110 +/- 17% to 86 +/- 22% (p less than 0.05) in the oestrogen therapy group. After orchidectomy there were no changes in the activators and inhibitors of coagulation and fibrinolysis studied as compared to base-line values. Furthermore the D dimer, a specific degradation product of crosslinked fibrin increased from a normal to a pathological value in 4 out of 8 tested patients after 6 weeks of oestrogen therapy, but in none out of 9 tested patients in the orchidectomy group. Briefly stated, patients with prostatic cancer treated with oestrogen have increased levels of factor VII, factor VIII:C and fibrinogen and a decreased level of antithrombin III.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbamazepine induced bradycardia--a problem in general or only in susceptible patients? A 24-h long-term electrocardiogram study.

Carbamazepine is a first line drug in the treatment of epilepsy and trigeminal neuralgia, but may exert negative chronotropic and dromotropic effects on the cardiac conduction system. Bradyarrhythmias of different types and severity have been described, especially in the elderly, but the prevalence of arrhythmias in a larger group of carbamazepine treated patients is unknown. Forty-eight patients, 40 years of older, on continuous carbamazepine treatment because of various neurologic disorders were investigated by interview, physical examination, 12-lead surface electrocardiogram, and 24-h long-term electrocardiogram recording. The prevalence of bradyarrhythmias was compared with that in an age-stratified reference group. There was no differences between the two groups, either in the number or the duration of pauses or in the type of pauses. In conclusion, carbamazepine does not increase the risk of bradyarrhythmias in the vast majority of patients.