Antiphospholipid syndrome and rheumatic fever: a case spanning three decades of changing concepts and common immunological mechanisms.

We present a case of primary antiphospholipid syndrome (APS), initially diagnosed as acute rheumatic fever, resulting in severe mitral valve incompetence. This case raises questions of the specificity of the Jones diagnostic criteria for rheumatic fever in a population where it is infrequently encountered. There are similarities in clinical, pathological and echocardiographic presentations between rheumatic fever and APS, in addition to common immunological mechanisms. Our case highlights the possibility that rather than rheumatic fever being primarily responsible for her recurrent attacks of chorea and arthritis, the streptococcal infections in our patient occurred either in the setting of underlying antiphospholipid antibodies ('second hit' phenomenon), or may have triggered the development of pathogenic antibodies (molecular mimicry), subsequently leading to the clinical evolution of APS. During the three decades of our patient and her recurrent problems, there has been an evolving knowledge of the mechanisms of APS and rheumatic fever, allowing us to extend our understanding beyond symptoms and syndromes, to a better realization of the underlying immunological relationship between the two.

Is Sydenham's chorea an antiphospholipid syndrome?

In 1686, Thomas Sydenham described a syndrome of chorea occurring in youth which was subsequently shown to be a complication of rheumatic fever. An association between chorea and antiphospholipid antibodies has been reported since 1985. We report two females presenting with chorea, aged 17 and 22, who fulfilled the Jones' criteria for rheumatic fever and concurrently had antiphospholipid antibodies detected in serum. A third patient presented at the age of 16 with two bouts of Sydenham's chorea; no assays for antiphospholipid antibodies were performed at the time but 13 years later she was found to have high titres of anticardiolipin antibodies. No patient had abnormalities in the basal ganglia detected on magnetic resonance imaging. Sydenham's chorea may be part of the spectrum of antiphospholipid-associated neurological disease.

Metolazone in treatment of severe refractory congestive cardiac failure.

17 patients with New York Heart Association (NYHA) class IV congestive cardiac failure, refractory to conventional treatment, were additionally treated with oral metolazone (1.25-10 mg daily). 12 improved sufficiently to be discharged from hospital (NYHA class II or III, mean weight loss 8.3 kg), 1 of whom died at home 4 weeks later. The other 5 patients were treated with intravenous dobutamine for 72 h; 2 responded (average weight loss 4.4 kg), and 2 responded to subsequent reintroduction of metolazone. 4 of these 5 patients died, 2 in hospital of acute myocardial infarction. Overall, 15 patients with very severe refractory cardiac failure improved sufficiently to be discharged from hospital. Treatment was associated with mild transient hypokalaemia in 7 patients, and hyponatraemia and renal impairment in 1, for whom metolazone dosage had to be reduced. Failure to respond to the introduction of metolazone may indicate an especially poor prognosis.

Mitral valve prolapse and retinal infarction.

Several neurological syndromes, including syncope, convulsions, amnesia, transient ischaemic attacks and cerebral infarction, have been associated with mitral valve prolapse. It has been presumed that emboli may account for some of these. We report a case of retinal infarction in association with mitral valve prolapse.

Detection of multivessel disease after myocardial infarction using intravenous stress digital subtraction angiography.

Forty-six patients with prior myocardial infarction underwent stress intravenous digital subtraction angiography (DSA) and coronary angiography. The left ventricular ejection fraction (EF) and wall-motion responses to exercise were correlated with the coronary anatomy. Twenty-five patients with single vessel disease showed essentially no change in left ventricular EF with exercise (a decrease from 66% to 64%), but those with multivessel disease (21 patients) had a significant decrease in left ventricular EF (from 59% to 48%) (P = .0001). A decrease in left ventricular EF had a sensitivity of 95% and specificity of 60% for the detection of multivessel disease, whereas an increase in wall-motion abnormality had a sensitivity and specificity of 72% and 71%, respectively. After myocardial infarction, a fall in left ventricular EF with stress intravenous DSA is highly sensitive for the detection of multivessel disease, but there are a number of false-positive results, resulting in only moderate specificity. A new wall motion abnormality has only a moderate sensitivity and specificity.

Prospective comparison of exercise digital subtraction and exercise first pass radionuclide ventriculography.

In order to test the comparative sensitivities of first-pass radionuclide and digital subtraction ventriculography in detecting wall motion abnormalities during exercise, 29 patients referred for coronary angiography were submitted to both types of stress ventriculograms. Resting and exercise ventriculograms by both techniques were reviewed by independent observers and the five equal ventricular wall segments were graded as normal, mildly, moderately, severely hypokinetic, akinetic, or dyskinetic. Of the 29 patients, 24 had arteriographically defined ischemic potential (at least greater than 50% obstruction of a major coronary artery supplying viable myocardium). Exercise digital subtraction ventriculography correctly identified 17 (71%) of these by a worsening of wall motion during exercise, while radionuclide ventriculography identified only eight (33%) by the wall motion response. When either a worsening of wall motion or the failure to increase ejection fraction by at least 5 points were used as criteria for an abnormal test, the sensitivities of digital and radionuclide ventriculographies were 96% and 79%, respectively. Though the number of patients without ischemic potential (5 patients) was too small to judge the relative specificities, digital subtraction ventriculography appears to be more sensitive than radionuclide ventriculography in identifying exercise-induced wall motion abnormalities and in predicting coronary occlusions.

Exercise digital subtraction ventriculography for the detection of ischaemic wall motion abnormalities in patients without myocardial infarction.

Digital subtraction angiography permits high resolution imaging of the left ventricle after an intravenous injection of contrast medium. The capacity of digital subtraction angiography to detect ischaemic wall motion abnormalities was tested in 150 consecutive patients without myocardial infarction who were referred for coronary angiography. Digital ventriculograms were considered to be abnormal if there was a severe wall motion abnormality at rest or if segmental wall motion deteriorated after exercise. The global ventricular response to exercise was considered to be abnormal if the ventricular ejection fraction computed by the Dodge area length formula was less than 50% at rest or failed to increase after exercise. Seventy eight (52%) of these subjects had stenosis of greater than 50% of at least one major coronary artery. In 36 (24%) more than one major coronary vessel was affected. Sensitivities for the detection of stenoses greater than 50% coronary obstruction were 82% and 69% for an abnormal segmental wall motion response and an abnormal ejection fraction response respectively. The specificity of these test responses was 76% and 68% respectively. No complications resulted from the digital ventriculographic studies. It is concluded that safe adequate digital ventricular imaging at rest and after exercise is possible and that an abnormal wall motion response is a sensitive indicator of important coronary obstructive disease.

The use of intravenous digital subtraction angiography in the evaluation of tetralogy of Fallot.

Sixteen patients with tetralogy of Fallot were studied with intravenous digital subtraction angiography (DSA). Of these, 11 were males and five were females, ranging in age from 26 months to 54 years, with a mean age of 22 years at the time of the initial study. Twenty-two DSA studies were performed in the 16 patients, in seven patients preoperatively, in 12 patients postoperatively, and in three patients both pre- and postoperatively. In the seven patients studied preoperatively, all DSA studies were considered technically adequate as corroborative evidence in the diagnosis of tetralogy of Fallot. All associated cardiac abnormalities were adequately demonstrated. The 16 postoperative studies on 12 patients were performed to evaluate the adequacy of the surgery and/or postoperative complications. These studies were judged as technically satisfactory. The authors utilized intravenous DSA in the pre- and postoperative evaluation of 16 patients with tetralogy of Fallot and found that reliable angiographic information was provided and that this technique may serve as a useful adjunct with other noninvasive and invasive tests in the preoperative and postoperative evaluation of these patients.

Cardiac cinefluoroscopy as an inexpensive aid in the diagnosis of coronary artery disease.

To compare the accuracy of cinefluoroscopy, exercise electrocardiography and thallium perfusion imaging in diagnosing coronary artery disease (CAD), these 3 studies were performed in 297 subjects without prior acute myocardial infarction who were referred for coronary angiography. Of the 137 patients who had more than 50% angiographic diameter narrowing in at least 1 major coronary artery, 91 (67%) were correctly identified by cinefluoroscopy, 90 (66%) by stress electrocardiography and 100 (73%) by thallium imaging. Of the 164 patients with no more than 50% diameter narrowing, the proportion of patients correctly identified as normal were 81%, 72% and 79%, respectively. Cardiac cinefluoroscopy correctly classified 74% of the 297 subjects as to their disease status (more than 50% coronary narrowing), compared to 69% for stress electrocardiography and 76% for thallium imaging. There was no significant difference between the sensitivity or specificity of the test combination of stress electrocardiography and cinefluoroscopy and the combination of stress electrocardiography and thallium imaging. Cardiac cinefluoroscopy, a relatively cost-effective diagnostic test, is similar in accuracy to other, more expensive noninvasive diagnostic examinations for CAD.

Bayesian analysis versus discriminant function analysis: their relative utility in the diagnosis of coronary disease.

Both Bayesian analysis assuming independence and discriminant function analysis have been used to estimate probabilities of coronary disease. To compare their relative accuracy, we submitted 303 subjects referred for coronary angiography to stress electrocardiography, thallium scintigraphy, and cine fluoroscopy. Severe angiographic disease was defined as at least one greater than 50% occlusion of a major vessel. Four calculations were done: (1) Bayesian analysis using literature estimates of pretest probabilities, sensitivities, and specificities was applied to the clinical and test data of a randomly selected subgroup (group I, 151 patients) to calculate posttest probabilities. (2) Bayesian analysis using literature estimates of pretest probabilities (but with sensitivities and specificities derived from the remaining 152 subjects [group II]) was applied to group I data to estimate posttest probabilities. (3) A discriminant function with logistic regression coefficients derived from the clinical and test variables of group II was used to calculate posttest probabilities of group I. (4) A discriminant function derived with the use of test results from group II and pretest probabilities from the literature was used to calculate posttest probabilities of group I. Receiver operating characteristic curve analysis showed that all four calculations could equivalently rank the disease probabilities for our patients. A goodness-of-fit analysis suggested the following relationship between the accuracies of the four calculations: (1) less than (2) approximately equal to (4) less than (3). Our results suggest that data-based discriminant functions are more accurate than literature-based Bayesian analysis assuming independence in predicting severe coronary disease based on clinical and noninvasive test results.

Verification of Fourier phase and amplitude values from simulated heart motion using a hydrodynamic cardiac model.

Using pusher-plate-type artificial hearts, changes in the degree of synchrony and stroke volume were compared to phase and amplitude calculations from the first Fourier component of individual-pixel time-activity curves generated from gated radionuclide images (RNA) of these hearts. In addition, the ability of Fourier analysis to quantify paradoxical volume shifts was tested using a ventricular aneurysm model by which the Fourier amplitude was correlated to known increments of paradoxical volume. Predetermined phase-angle differences (incremental increases in asynchrony) and the mean phase-angle difference calculated from RNAs showed an agreement of -7 degrees +/- 4.4 degrees (mean +/- SD). A strong correlation was noted between stroke volume and Fourier amplitude (r = 0.98; P less than 0.0001) as well as between the paradoxical volume accepted by the 'aneurysm' and the Fourier amplitude (r = 0.97; P less than 0.0001). The degree of asynchrony and changes in stroke volume were accurately reflected by the Fourier phase and amplitude values, respectively. In the specific case of ventricular aneurysms, the data demonstrate that using this method, the paradoxically moving areas may be localized, and the expansile volume within these regions can be quantified.

Prediction of improvement in left ventricular function after ventricular aneurysmectomy using Fourier phase and amplitude analysis of radionuclide cardiac blood pool scans.

Postoperative improvement in left ventricular (LV) function is a common objective of LV aneurysmectomy, but is difficult to predict. The first Fourier component of time-activity curves of pre- and postoperative gated radionuclide angiographic studies was evaluated for this purpose in 20 patients who had undergone aneurysmectomy. LV aneurysms had portions that characteristically exhibited marked phase delay with varying degrees of amplitude. Total aneurysmal amplitude was obtained preoperatively by summing the amplitude component of all pixels that exhibited phase delay, suggesting paradoxical motion. LV ejection fraction (EF) before and after aneurysmectomy and the absolute postoperative increase in LVEF were calculated. Nine of 20 patients had an absolute increase of EF less than 10% despite resection of large aneurysms. A strong correlation was found between the absolute increase in EF after aneurysmectomy and the total amplitude within paradoxically moving areas (r = 0.93, p less than 0.0001). Thus, preoperative measurement of the total paradoxical amplitude predicts absolute change in EF and may be important in selecting patients for aneurysmectomy. The data also suggest that the total aneurysmal amplitude reflects the stroke volume ejected into an aneurysm in systole and that paradoxical expansion of an aneurysm contributes to LV dysfunction in some of these patients.

Variant angina: comparison of patients with and without fixed severe coronary artery disease.

To determine if the clinical features of variant angina are predictive of the severity of underlying coronary artery disease, 43 patients with variant angina who had less than 50% fixed coronary luminal diameter narrowing (group 1) were compared with 65 patients with variant angina who had 70% or greater diameter narrowing (group 2). Statistically significant differences were found in 3 clinical features between group 1 and group 2: (1) a more than 3-month history of angina at rest before diagnosis (80% vs 23%, p less than 0.001); (2) an abnormal electrocardiogram at rest (19 vs 48%, p less than 0.01); and (3) an abnormal stress test (26% [8 of 30] vs 84% [15 of 18], p less than 0.01). However, these features were not clinically reliable in separating patients with variant angina with and without fixed severe obstructions because of overlap between the 2 groups. No difference was found between the 2 groups in age, sex, predominant symptom at the time of catheterization, history of exertional angina, syncope with angina, prolonged angina, previous myocardial infarction or risk factors for coronary artery disease. There was also no difference in the location of ST elevation or occurrence of major arrhythmias during angina. Thus, among patients with Prinzmetal's variant angina, those with normal or mildly abnormal coronary arteriograms cannot be differentiated reliably by clinical features from those with fixed severe coronary obstructions. Coronary arteriography should be performed to define the underlying coronary anatomy and to determine optimal therapy in patients with variant angina.

Intravenous digital subtraction angiography in the assessment of patients with left to right shunts before and after surgical correction.

Pre- and postoperative structural changes and pulmonary to systemic flow (QP/QS) ratios were assessed using digital angiography in 34 patients documented to have a left to right shunt at cardiac catheterization. There were 16 men and 18 women whose ages ranged from 4 months to 60 years. The radiographic single mask mode was used for all digital subtraction angiographic studies with a typical radiographic sequence being 80 to 100 kV, 5 to 10 mA/frame at six frames/s for 15 seconds. Renografin-76 was used as a bolus injection at 0.5 to 1.0 ml/kg via an arm vein in most patients. The level of the left to right shunt and any associated anomalies were noted and compared with results from cardiac catheterization. Digital subtraction angiographic flow curves were generated from the pulmonary arteries, and QP/QS ratios were calculated pre- and postoperatively using the gamma variate fit method and compared with the QP/QS ratio from first pass radionuclide studies. A strong correlation between preoperative digital subtraction angiographically derived QP/QS ratio and radionuclide-derived QP/QS ratio was found, with an r value equal to 0.89, p less than 0.0001. Postoperatively, all patients had a QP/QS ratio less than 1.2:1.0 for both digital subtraction angiography and radionuclide studies. The level of left to right shunt was accurately assessed in all patients, and its absence observed postoperatively. Associated anomalies, such as a persistent left superior vena cava, coarctation of the aorta and partial anomalous venous return, were identified in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)