Systemic embolism in chronic left ventricular aneurysm: incidence and the role of anticoagulation.

The incidence and prevention of systemic embolism in patients with chronic left ventricular aneurysm have been controversial. This retrospective study investigated the incidence of clinically evident embolic events and the effect of oral anticoagulation in patients with unequivocal angiographically defined left ventricular aneurysm. Between 1971 and 1979, 76 patients met the ventriculographic criteria and received initial medical management. The median interval from myocardial infarction to ventriculography was 11 months (range 1 month to 16 years) and subsequent median follow-up time was 5 years. Twenty patients receiving anticoagulant therapy were followed up for a total of 40 patient-years and 69 patients not on anticoagulant therapy were followed up for a total of 288 patient-years; 13 patients were included in both subsets. Twenty-eight patients died during follow-up and the 3 and 5 year survival rates were 75 and 61%, respectively. Only one patient not receiving anticoagulant therapy had a clinical embolic event, resulting in an incidence of 0.35 per 100 patient-years. Therefore, in the absence of other predisposing conditions, the extremely low incidence of systemic emboli in these patients with chronic (first documented at least 1 month after myocardial infarction) left ventricular aneurysm does not justify the use of long-term oral anticoagulant therapy.

Progression of peripheral occlusive arterial disease in diabetes mellitus. What factors are predictive?

The clinical, biochemical, and vascular laboratory measurements potentially associated with the development and/or progression of peripheral occlusive arterial disease (POAD) were assessed during a 4-year period in 110 normal control subjects, 112 patients with POAD without diabetes mellitus, 240 patients with diabetes mellitus without POAD, and 100 patients with diabetes mellitus and POAD. Age, history of hypertension or coronary heart disease, history of cigarette smoking, presence of POAD, systolic blood pressure, and beta-thromboglobulin level were associated with progression of POAD. A multivariate logistic regression model indicated that the presence of diabetes mellitus or POAD or both at baseline, decreased postexercise ankle-brachial index, increased arm systolic blood pressure, and current smoking were independently associated with progression of POAD. This study suggests that cessation of smoking and control of hypertension are essential treatment modifications to decrease the risk of progression of peripheral vascular disease in diabetic patients.

Deep venous thrombosis and pulmonary embolism. Risk of subsequent malignant neoplasms.

We conducted a noncurrent prospective study of all Olmsted County, Minnesota, residents who had had a lower-extremity venogram, pulmonary angiogram, or lung scan performed because of suspicion of deep venous thrombosis or pulmonary emboli. One hundred thirteen cancer-free patients were followed for 386 person-years from the date of procedure. Nine subsequent cancers were observed compared with 4.5 expected (relative risk, 2.0; 95% confidence interval, 0.9 to 3.8), using total cancer incidence rates for the Rochester, Minn, population. Five hundred seventeen cancer-free controls were followed for 2072 person-years. Twenty subsequent cancers were observed compared with 11.6 expected, yielding a relative risk of 1.7 (95% confidence interval, 1.1 to 2.7). When cases and controls were compared directly, no statistically significant difference in cancer-free survival was found.

Course of peripheral occlusive arterial disease in diabetes. Vascular laboratory assessment.

To determine comparative rates of development and progression of peripheral occlusive arterial disease, 110 healthy nondiabetic control subjects, 112 patients with peripheral occlusive arterial disease (POAD), 240 patients with diabetes mellitus (DM), and 100 patients with diabetes mellitus and peripheral occlusive arterial disease (DM + POAD) were studied over 4 yr with noninvasive techniques. The presence of peripheral occlusive arterial disease was determined by postexercise ankle-brachial index (ABI) values; progression of peripheral occlusive arterial disease was determined by the rate of change in postexercise ABI. Patients who underwent peripheral arterial reconstructive surgery or amputation were also classified as having progression of their peripheral occlusive arterial disease. On this basis, follow-up revealed that peripheral occlusive arterial disease developed and therefore progressed in 1 (1%) of the control group and 22 (9%) of the DM. Peripheral occlusive arterial disease progressed in 31 (28%) of the POAD and 26 (26%) of the DM + POAD. The presence of peripheral occlusive arterial disease predisposes to progression of disease, and peripheral occlusive arterial disease is more likely to develop in diabetic patients who do not have peripheral occlusive arterial disease than in nondiabetic control subjects. However, the presence of diabetes mellitus in patients with peripheral occlusive arterial disease does not seem to increase the risk of progression.

Takayasu arteritis. A study of 32 North American patients.

Thirty-two patients (26 female, 6 male) with angiographically diagnosed Takayasu arteritis were seen at the Mayo Clinic between 1971 and 1982. Racial composition of this group was 23 North American Caucasians, 4 Mexicans, 3 Orientals, 1 Native American, and 1 patient of Middle Eastern origin. Incidence of the disease in Olmsted County, Minnesota, was 2.6/million/year. Diagnosis was often delayed for long periods of time, with a median delay of 18 months. Patients had both non-vascular symptoms (arthralgias in 56%, fever in 44%, weight loss in 38%) and symptoms of vascular stenosis such as arm claudication (47%) and hypertension due to renal artery stenosis (41%). All patients had either multiple vascular bruits (94%) or absent pulses (50%). Laboratory findings included anemia (44%) and elevations of erythrocyte sedimentation rate (78%). Almost all patients had multiple sites of arterial involvement documented by angiogram with various combinations of stenosis, luminal irregularity and aneurysm formation. Response to corticosteroid treatment was usually very good, with dramatic improvement in non-vascular symptoms and return of pulses in 8 of the 16 patients with absent pulses prior to treatment. Five-year survival rate from time of diagnosis was 94%. Twelve patients underwent surgical procedures involving the carotid arteries (5 cases), subclavian artery (4 cases) and renal arteries (3 cases). Three aneurysms were resected, one had aortic valve replacement for severe aortic regurgitation, and two patients underwent transluminal angioplasty. Pathologic changes were restricted to the media and adventitial layers of the vessel wall and were indistinguishable from those of giant-cell or temporal arteritis. Takayasu arteritis is more common than previously suspected in North America, is not restricted to any one racial group, and is readily treatable with corticosteroids and surgical vascular reconstruction.

Venous air embolism. Life-threatening complication of orogenital sex during pregnancy.

Vaginal insufflation in pregnant women leading to acute venous air embolism has been appreciated by obstetricians and pathologists for several decades. Initially described as a complication of powder insufflation for treatment of trichomonal vaginitis, insufflation-induced air embolism has been more recently associated with orogenital sex. The case herein illustrates a typical history that is almost pathognomonic. Clinical and laboratory abnormalities as well as treatment measures are briefly described. Familiarity with this syndrome is essential if prompt and appropriate therapy is to be rendered.

Cardiovascular complications of pheochromocytoma crisis.

Two patients with hypertensive crises due to pheochromocytoma presented with unusual features suggestive of cardiovascular disorders other than pheochromocytoma. These features included transient cortical blindness and other neurologic deficits, electrocardiographic changes indicative of transmural infarction and peripheral arterial spasm. In both patients the diagnosis of pheochromocytoma was made later; removal of the tumor was followed by ready reversal of the clinical and biochemical abnormalities. Management of such cases includes suspicion of the diagnosis in the presence of atypical features, early initiation of therapy with alpha and beta adrenergic blocking agents and a definitive surgical procedure before peripheral vascular changes become irreversible. When an apparent myocardial infarction occurs, the diagnosis of coronary artery disease cannot always be excluded, but rapid stabilization of the clinical and electrocardiographic changes after adrenergic blockade would favor the diagnosis of a catecholamine-induced myocarditis. The coexistence of coronary artery disease and uncontrollable arrhythmias presents an increased risk but, if pheochromocytoma is suspected, surgery may be necessary despite the increased risk.

A significant interaction between metronidazole and warfarin.

Interaction between metronidazole (Flagyl) and warfarin had been suggested based on the disulfiram-like effect of metronidazole and the known interaction of warfarin and disulfiram. This case report confirms that this interaction is clinically significant in man.

The penetrating aortic ulcer: pathologic manifestations, diagnosis, and management.

The term "penetrating aortic ulcer" refers to an ulceration of an atheromatous plaque that extends deeply through the intima and into the aortic media. It may precipitate an intramedial dissection (usually localized) or may rupture into the adventitia to form a pseudoaneurysm. The typical patient with penetrating atheromatous aortic ulcer is elderly and has hypertension, atherosclerosis, and back or chest pain, but pulse deficit, stroke, aortic insufficiency, and compromise of a visceral vessel are not present. Classic aortic dissection and symptomatic thoracic aortic aneurysms are among possibilities in the differential diagnosis. Aortography demonstrates the presence of an aortic ulcer similar in appearance to gastric ulcers seen on barium examination; in addition, an intramural aortic hematoma may be present. Our experience with penetrating aortic ulcers in symptomatic patients indicates that conservative medical therapy leads to recurrence of symptoms and a need for surgical intervention. We present a case that illustrates the salient features of this distinct clinical entity.

A prospective study of peripheral occlusive arterial disease in diabetes. I. Clinical characteristics of the subjects.

This paper describes the clinical characteristics of a group of normal control subjects, patients with clinical peripheral occlusive arterial disease, patients with diabetes and no clinical peripheral arterial disease, and patients with diabetes and peripheral arterial disease at the time of the enrollment of all subjects in a 5-year study of the factors involved in the progression of peripheral occlusive arterial disease in diabetes. Obesity and hypertension were more common in subjects with diabetes or peripheral occlusive arterial disease (or both) than in the control subjects. Smoking was more common in both groups with occlusive arterial disease than in those without it. The diabetic patients with occlusive arterial disease had a longer duration of diabetes mellitus and a higher rate of other diabetic complications than those without arterial disease.

Cardiomyopathy in patients with hereditary motor and sensory neuropathy.

Twelve affected persons in the third decade of life or later, and the 14 nearest age- and sex-matched unaffected relatives, of a large kindred with autosomal dominant hereditary motor and sensory neuropathy not linked to the Duffy blood group (HMSN type IA) were assessed for arrhythmia and cardiomyopathy. Cardiac abnormalities were no more frequent in the affected persons than in the unaffected relatives. The heart of a patient with HMSN type II who had died of complications of cardiomyopathy was found to have rheumatic disease-type myocarditis with Aschoff bodies. The results of this study provide further evidence against an association of cardiomyopathy and HMSN.

Optic neuropathy and amiodarone therapy.

Optic neuropathy has been diagnosed in several amiodarone-treated patients, including the 13 patients described in this report. The clinical severity of this drug-related optic neuropathy is milder than that characteristically described in anterior ischemic optic neuropathy. The incidence of occurrence was significantly higher than that found in an age-matched general population sample. Whether this result was due solely to amiodarone therapy, to the underlying poor health of these patients, or to a combination of these two factors is uncertain. The findings in this study prompt us to recommend that all patients who receive amiodarone undergo complete ophthalmologic examinations, including careful evaluation of the ocular fundus regularly during such therapy. Appearance of optic neuropathy is probably a relative indication for discontinuing the use of the drug, in the hopes of avoiding bilateral involvement or perhaps recovering vision. The risks of complications of amiodarone treatment must be weighed against the benefit of therapy in patients whose lives are threatened by cardiac arrhythmias. On the basis of this study, the benefits of treatment seem to outweigh the small risk of optic neuropathy. No randomized study has been undertaken to determine the true incidence of complications associated with this medication and at this time could not be justified.

Skin fibrinolytic activity in cutaneous and systemic vasculitis.

Study of involved and uninvolved skin from patients with necrotizing vasculitis revealed diminished tissue fibrinolytic activity deposition of immunoreactants in involved skin. In these patients, the depletion of tissue fibrinolytic activity is probably the result of vessel injury secondary to the local deposit of immunoreactants. In addition, there was diminished tissue fibrinolytic activity in uninvolved skin from patients with and without clinical skin involvement, unassociated with the deposition of immunoreactants. The precise mechanism for diminished tissue lytic activity in these latter patients is not known, but it may be associated with generalized activation of the coagulation and fibrinolytic mechanisms that result in local depletion of tissue fibrinolytic activity. These local changes may aggravate the clinical course of the disease as well as inhibit the healing of the lesions.

Heparin-induced thrombocytopenia and thrombosis in ischemic stroke.

We reviewed the records of all patients who underwent carotid endarterectomy at our institution during the period from January 1970 through December 1986 to determine the frequency of postoperative occlusions and the role of heparin-induced thrombosis in patients with such occlusions. After 2,527 carotid endarterectomies, a total of 19 occlusions occurred in 18 patients. Of these 18 patients, 6 had an associated heparin-induced coagulation disorder, 3 of whom are described in detail. Although heparin is a useful anticoagulant, it may precipitate occlusion of vessels after an endarterectomy procedure, either at the endarterectomy site or elsewhere. Physicians should be aware of the potentially increased risk for embolic or thrombotic cerebrovascular events in patients who receive heparin therapy.

Management of hemophilia A and B during surgical correction of transposition of the great arteries.

Two patients--one an infant and the other an adolescent--with transposition of the great arteries and hemophilia underwent a successful major reconstructive open-heart surgical procedure. Despite a severe coagulation deficiency, a major reconstructive cardiac operation was performed with the use of a detailed replacement plan, which took into consideration the potency of the replacement material and its potential hazards, biologic half-life, and anticipated in vivo recovery on the basis of the patient's plasma volume. To our knowledge, these are the first reports of successful surgical repair of this type in patients with severe coagulation factor deficiency.

A prospective study of peripheral occlusive arterial disease in diabetes. IV. Platelet and plasma functions.

Platelet factor 4-like activity, circulating platelet-aggregate ratios, ristocetin cofactor, Willebrand antigen, ADP-induced platelet aggregation-enhancing factor, and quantitative platelet aggregation response to ADP, epinephrine, and collagen in platelet-rich plasma were measured in four groups of subjects with similar age and sex distribution. Neither platelet factor 4-like activity nor circulating platelet-aggregate ratios differentiated these four groups. Platelet aggregation studies with ADP a subthreshold concentration support the concept of hypersensitivity of diabetic platelets in males. Male and female subjects differ significantly in their quantitative response to aggregating agents when such studies are done under similar conditions. Willebrand factor activity and Willebrand antigen normally increase with age. Elevation in these activities above that accounted for by age characterizes the presence of vascular disease but not diabetes mellitus in the absence of vascular disease. A plasma factor enhancing platelet aggregation could not be demonstrated in most diabetic patients in this study.

Factor VIII-von Willebrand factor in giant cell arteritis and polymyalgia rheumatica.

Levels of three factor VIII-von Willebrand factor components (von Willebrand antigen, ristocetin cofactor, and factor VIII coagulant) were higher in specimens of plasma from 27 patients with giant cell arteritis and 18 patients with polymyalgia rheumatica than in specimens from 21 normal control subjects. Values in patients with active giant cell arteritis were higher than those in patients with either inactive giant cell arteritis or active polymyalgia rheumatica. Levels of factor VIII-von Willebrand factor components tended to decline gradually after disease activity had been suppressed by corticosteroid therapy and therefore may be indicators of vascular damage. These levels, however, did not revert to normal rapidly in response to corticosteroid therapy as did the patients' symptoms and the usual laboratory measurements indicative of inflammation; thus, measurements of these components are unlikely to be useful in day-to-day management of these diseases. Electrophoretic analysis suggested that the elevated values are due to increased amounts of normal factor VIII-von Willebrand factor rather than to the presence of an abnormal molecule.

A prospective study of peripheral occlusive arterial disease in diabetes. III. Initial lipid and lipoprotein findings.

Lipid and lipoprotein findings are described in a group of 707 persons consisting of normal control subjects, patients with clinical peripheral occlusive arterial disease, patients with diabetes and no occlusive arterial disease, and diabetic patients with occlusive arterial disease. The mean serum triglycerides were elevated in all groups compared with the normal controls and varied, depending on the type and treatment of the diabetes and fasting plasma glucose concentration. Mean total serum cholesterol did not change among the groups. Unexpectedly, the mean level of low-density lipoprotein cholesterol was significantly lower in patients with diabetes who had no occlusive arterial disease than in normal subjects. The mean high-density lipoprotein cholesterol level was higher in normal-weight, insulin-treated diabetic patients than in obese diabetics regardless of their treatment. Disturbances in triglyceride metabolism and the related lipoproteins appear to characterize both diabetes and occlusive arterial disease, with the highest mean levels of serum triglycerides being found in subjects with both diabetes and occlusive arterial disease.

A prospective study of peripheral occlusive arterial disease in diabetes. II. Vascular laboratory assessment.

Noninvasive tests of the peripheral circulation were used to quantify the presence and severity of occlusive arterial disease in the lower extremities in 707 subjects on entry into a prospective study. Four groups were studies: 124 normal subjects, 157 patients with clinically evident occlusive arterial disease, 295 patients with diabetes mellitus without clinically evident occlusive arterial disease, and 131 patients with diabetes mellitus and clinically evident occlusive arterial disease. The lower extremity-to-arm systolic blood pressure ratios at rest, ankle-to-arm systolic blood pressure ratios after exercise, and segmental plethysmographic recordings accurately identified the groups with occlusive arterial disease and quantified the spectrum of severity in each of the groups. The 1-minute postexercise ankle-to-arm systolic blood pressure ratio was the single best indicator in discriminating between normal subjects and patients with occlusive arterial disease. The exercise electrocardiogram was positive in 30 of the 583 patients and in none of the group of normal subjects. The systolic blood pressure was falsely elevated as a result of sclerotic, noncompressible arteries in the segment of the limb under the pneumatic cuffs in 12 of the patients but in none of the normal subjects.

Solitary renal artery aneurysm.

The records of all patients with solitary renal artery aneurysms seen between January 1968 and December 1978 were reviewed. Patients with fibromuscular dysplasia were excluded from analysis. Of the 67 patients seen, 34 had the diagnosis made on the basis of arteriography, 31 on the basis of abdominal roentgenography, and 2 at surgery. The ages of the 67 patients (34 men and 33 women) ranged from 21 to 90 years, with a mean of 61 years. Only five patients (8%) were symptomatic; all five presented with abdominal pain. Forty-six patients (69%) had associated hypertension. Five patients underwent surgical repair when initially seen. Only one patient had preoperative abdominal pain that was considered to be related to the aneurysm. The aneurysm sizes ranged from 0.3 to 4.0 cm, with a mean of 1.5 cm. In 45 patients (67%) the aneurysm was calcified. Follow-up ranged from 1 to 17 years, with a mean 5.7 and a median of 8.0 years. During follow-up, all aneurysms remained clinically silent. No aneurysms were subsequently repaired, no new cases of hypertension developed, no nephrectomies had to be performed, and no ruptures occurred. Eight patients (12%) died; no death was related to a complication of the aneurysm. This study supports the view that patients with asymptomatic solitary saccular renal artery aneurysm may be safely observed without surgical intervention.