The enhancement of macrophage bacteriostasis by products of activated lymphocytes.

It was reported previously that the incubation of normal guinea pig macrophages with partially purified products of activated lymphocytes resulted in altered macrophage function including increased cell adherence to culture vessels, spreading, phagocytosis, and glucose carbon-1 oxidation. Studies reported here demonstrate that such macrophages also exhibit enhanced bacteriostasis. Lymphocytes were stimulated with concanavalin A, the culture supernatant was chromatographed over Sephadex G-100 and the fraction of mol wt 25,000-55,000, rich in lymphocyte mediators, was cultured with normal guinea pig macrophages for 1-3 days. Macrophages incubated with fractions from unstimulated lymphocyte cultures served as controls. The resulting macrophage monolayers were infected with Listeria monocytogenes. Macrophages incubated with mediator-rich fractions exhibited 2- to 10-fold enhanced bacteriostasis compared to controls. Further studies indicate that this enhancement was attributable to intrinsic changes in the macrophages and not simply a consequence of the number of macrophages on the monolayers. The studies support the concept that macrophage bacteriostasis can be enhanced by lymphocyte mediators. However, macrophages, which have been preincubated directly with sensitive lymphocytes and antigen exhibit even greater bacteriostasis and sometimes bactericidal capacity, suggesting that either a labile lymphocyte factor or direct lymphocyte macrophage interaction may also be involved in bactericidal activity.

Coronary artery spasm in the denervated transplanted human heart: a clue to underlying mechanisms.

The mechanism of coronary artery spasm has been poorly understood but there has been some suggestion that cardiac autonomic innervation may play an important role. We report coronary artery spasm in a 43 year old man two years after he had received a transplant. Provocative pharmacologic testing suggested functional denervation of the patient's heart. Thus, coronary artery spasm can occur in the transplanted, denervated human heart. Autonomic innervation of the heart is not essential in all cases of coronary spasm, and circulating catecholamines and/or metabolic of hormonal products may play an important role.

Left ventricular function at high altitude examined by systolic time intervals and M-mode echocardiography.

To better understand the effects of high-altitude hypoxia on cardiac performance, healthy lowland-residing volunteers were studied in 2 groups: 10 subjects after acute ascent to 12,500 ft (3,810 m) (acute group) and 9 subjects after chronic exposure for 6 weeks to 17,600 ft (5,365 m) and 11,000 ft (3,353 m) (chronic group). Systolic time intervals and M-mode echocardiograms were recorded at low and high altitudes. Heart rate was 21% greater at high altitude for all subjects. Preejection period/left ventricular ejection time (PEP/LVET) increased by 16% in the acute group and by 22% in the chronic group. Heart size was smaller at high altitude in both groups, with left atrial and left ventricular (LV) diameters decreasing by 10 to 12%. These changes were statistically significant (p less than or equal to 0.01). Despite the increase in PEP/LVET, echocardiographic measurements of LV function (percent fractional shortening and mean normalized velocity of circumferential fiber shortening) remained normal. LV isovolumic contraction time was shorter at high altitude, suggesting heightened, rather than depressed, contractility. LV function does not appear to deteriorate at high altitude. Alterations in systolic time intervals probably result from decreased preload, as reflected by smaller heart size, rather than from heart failure or depressed LV contractility.

Aortitis in ankylosing spondylitis: early detection of aortic root abnormalities with two dimensional echocardiography.

Mild aortic root dilatation, cusp thickening and subvalvular fibrous ridges have been reported as characteristic in patients with ankylosing spondylitis and aortic regurgitation. Thirty-five patients with ankylosing spondylitis (10 also had Reiter's syndrome) without clinically apparent cardiac involvement were studied using phased array two dimensional and sector-directed M mode echocardiography to determine the prevalence of aortic abnormalities. Aortic root dimensions were measured at the aortic anulus, at the tip of the cusps and 0.5 to 1.5 cm above the cusps. The two dimensional echocardiographic study was also analyzed for qualitative abnormalities. The dimensions were compared with those in 20 normal men and among patient subgroups separated according to age, duration and severity of ankylosing spondylitis and presence of qualitative abnormalities. With one exception, no abnormally increased aortic dimensions suggestive of aortic dilatation were found in any group. However, two patients had aortic dimensions greater than 4.2 cm at the valve (normal 4.0 cm or less). Also, six patients had discrete areas of increased bright echoes below the left or noncoronary cusps suggestive of a subaortic "bump" and two of the six patients had increased aortic cusp echoes suggestive of thickening or fibrosis, or both. These changes tended to occur more commonly in older patients and those with more severe disease. It is concluded that aortic root changes suggestive of inflammation or fibrosis, or both, occur in asymptomatic patients with ankylosing spondylitis and are detectable on two dimensional echocardiography. Dilatation usually does not occur without aortic regurgitation.

Patients with congestive cardiomyopathy as cardiac transplant recipients. Indications for and results of cardiac transplantation and comparison with patients with coronary artery disease.

In recent years end-stage congestive cardiomyopathy has become an increasingly frequent clinical diagnosis in candidates for cardiac transplantation. Forty-six patients who underwent transplantation because of congestive cardiomyopathy and 59 because of coronary artery disease were studied between 1971 and 1978 at Stanford University. The overall 1 year survival rate was similar in the two groups: cardiomyopathy-transplant, 64 percent and coronary artery disease-transplant, 55 percent. The survival rate has improved substantially for both groups within the last decade: The 3 year survival rate for cardiomyopathy-transplant patients undergoing cardiac transplantation since 1974 is nearly 60 percent. In contrast, 36 similarly ill patients with cardiomyopathy not undergoing transplantation had a 1 year survival rate of 23 percent and a 3 year survival rate of 4 percent (p less than 0.001). Survival rates in the cardiomyopathy-transplant group were unaffected by age (greater or less than 40 years). Patients in this group under age 40 had a lower frequency of infection (1 per 313 patient-days versus 1 per 195 patient-days in the older group, p less than 0.05) and a significantly longer interval to second rejection episodes (p less than 0.05), a measure of rejection frequency. Cardiomyopathy-transplant patients under age 40 had fewer deaths due to rejection (17 percent) compared with older patients in this group (36 percent). Cardiac transplantation is an effective treatment for end-stage congestive cardiomyopathy.

Single and two dimensional echocardiographic features of the interatrial septum in normal subjects and patients with an atrial septal defect.

The interatrial septum is one of the least studied structures in M mode echocardiography. Two dimensional echocardiography has made it possible to record simultaneous M mode and two dimensional echocardiograms. Such studies were performed in 10 normal subjects and in 9 patients with a secundum atrial septal defect. In the short axis view of the base of the heart, the interatrial septum was visualized in the two dimensional studies as a linear echo running from the posterior aortic wall to the posterior atrial wall and in the M mode records as a series of dense echoes posterior to the aorta. The great variability in echo dropout of the interatrial septum made it impossible to distinguish the normal subjects from the patients with atrial septal defect. The dense echoes of the interial septum in the M mode records gave the false impression that they were filling the left atrium. These data indicate that (1) a secundum atrial septal defect cannot be reliably differentiated from a normal septum using these echocardiographic methods, and (2) the medial location of the interatrial septum should be appreciated so that it will not be confused with a left atrial mass.

Effect of coronary arterial bypass surgery on exercise-induced ventricular arrhythmias. Long-term follow-up of a prospective randomized study.

The effect of coronary arterial bypass surgery on exercise-induced ventricular arrhythmias and their relation to sudden death was examined in 102 patients with stable angina pectoris randomly assigned to medical and surgical therapy (54 and 48 patients, respectively). Symptom-limited treadmill tests were performed at entry and at 1 and 5 years. The surgical group demonstrated significant improvement in exercise performance at 1 year compared with the medical group, and at 5 years exercise-induced ischemia as evidenced by S-T depression and exertional angina remained substantially decreased in the surgical group with little change in the medical group. However, the frequency and severity of exercise-induced ventricular arrhythmias in each group remained unchanged at 1 and 5 years from those at entry. Similar results were obtained from an evaluation of ventricular arrhythmias in the electrocardiogram at rest. With the exception of exercise-induced ventricular tachycardia and fibrillation, no relation was found between ventricular arrhythmias and sudden death. Coronary bypass grafting does not decrease the frequency or severity of exercise-induced or resting ventricular arrhythmias. In patients with stable angina pectoris, with the exception of ventricular tachycardia and fibrillation, exercise-induced ventricular arrhythmias are poor predictors of sudden death. The data suggest that exercise-induced ventricular arrhythmias may not be related to ischemia but to other effects of exercise such as cardiac stimulation by catecholamines or other factors.

Two dimensional echocardiographic assessment of patients with bioprosthetic valves.

The clinical utility of two dimensional echocardiography in assessing bioprosthetic and left ventricular function was studied in 40 consecutive patients 1 week to 60 months after valve replacement surgery. These patients were referred to obtain normal baseline studies as well as to evaluate complications:suspected endocarditis, embolic phenomena and congestive heart failure of unknown cause. Independent M mode echocardiograms were also obtained in each patient. Confirmation of ultrasonic studies was by cardiac catheterization with angiography, surgery and pathologic study in 10 patients; cardiac catheterization with angiography alone in 7 patients; surgery and pathologic study in 3 patients; autopsy in 3 patients; blood cultures to confirm or exclude endocarditis in 10 patients; and confirmation on clinical grounds in 7 patients. Technically adequate two dimensional studies were recorded in 39 of 40 subjects. Two dimensional echocardiography accurately assessed 15 of 16 patients with an abnormal bioprosthetic valve and a normal left ventricle (1 of 16 patients had a false positive two dimensional echocardiogram); 8 of 8 patients suspected to have prosthetic valve or left ventricular dysfunction but who were normal; 7 of 7 patients with a normal prosthesis and an abnormal left ventricle; the one patient with an abnormal valve and left ventricle; and 7 of 7 clinically normal patients who were referred for baseline studies. In summary, the two-dimensional echocardiogram demonstrated a 97 percent diagnostic accuracy rate which was significantly greater than the 67 percent (P less than 0.001) for M mode echocardiography in the same group of patients. It is concluded that two dimensional echocardiography has excellent diagnostic accuracy in assessing bioprosthetic and left ventricular function and is superior to M mode echocardiography in evaluating patients after such valve replacement.

Spontaneous dissection of the ascending aorta diagnosed by two-dimensional echocardiography.

In two patients with acute dissection of the ascending aorta, the diagnosis was made with two-dimensional echocardiography and confirmed by aortography. The echocardiograms localized the intimal flap and false channel in both cases. Although clinical evaluation and indicated radiologic studies remain the primary modalities of diagnosis in acute aortic dissection, two-dimensional echocardiography may be a useful additional diagnostic technique.

Two-dimensional echocardiographic features of bicuspid aortic valve.

The two-dimensional cross-sectional echocardiographic diagnosis of bicuspid aortic valves is described and compared with results of M-mode echocardiograms. Aortic valve anatomy was determined in 19 selected patients by angiography, and confirmed in five by direct surgical visualization. Using an eccentricity index (EI) of 1.3 or greater as diagnostic of bicuspid aortic valve, M-mode correctly identified anatomy in 14 of 19 valves (74 percent), although EI varied in several patients. For two-dimensional diagnosis of bicuspid aortic valve, short axis cross section was preferred, and criteria included number of cusps seen in real time motion, irregularity of folding of cusp margins, and location of commissural insertions. Two-dimensional echocardiography correctly identified anatomy in 18 of 19 valves (95 percent). Long axis cross section disclosed valvular doming in all 8 patients in whom doming was observed angiographically, correlating with hemodynamic findings. Two-dimensional echocardiography aids in the detection of bicuspid aortic valve in a suspected population, can give an estimate of valve gradients, and explains variability in M-mode findings. As such, two-dimensional echocardiography is a valuable tool in the noninvasive diagnosis of the bicuspid aortic valve.

Lisinopril versus placebo in the treatment of heart failure: the Lisinopril Heart Failure Study Group.

Lisinopril, a long-acting, angiotensin-converting enzyme inhibitor, was compared with placebo in a randomized, parallel, double-blind, 12-week study of 193 patients with heart failure. All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics. After 12 weeks of therapy, the improvement in treadmill exercise duration was greater in the lisinopril group (113 seconds) compared with the placebo group (86 seconds). This improvement in exercise duration was particularly evident in patients with left ventricular ejection fractions less than 35% (lisinopril = 130 seconds; placebo = 94 seconds). In patients receiving lisinopril, the increase in exercise duration was accompanied by an improvement in quality of life as measured by the Yale Scale Dyspnea/Fatigue Index and in signs and symptoms of heart failure. In addition, the lisinopril group had a larger mean increase (3.7%) in left ventricular ejection fraction when compared with the placebo group (1.3%). Thus, lisinopril, administered once daily for 12 weeks, was well tolerated and efficacious in the treatment of heart failure when used concomitantly with diuretics and digoxin.

Femoral arterial puncture management after percutaneous coronary procedures: a comparison of clinical outcomes and patient satisfaction between manual compression and two different vascular closure devices.

BACKGROUND: Vascular access site management is crucial to safe, efficient and comfortable diagnostic or interventional transfemoral percutaneous coronary procedures. Two new femoral access site closure devices, Perclose and Angio-Seal , have been proposed as alternative methods to manual compression (MC). We compared these two devices and tested them in reference to standard MC for safety, effectiveness and patient preference. METHODS: Prospective demographic, peri-procedural, and late follow-up data for 1,500 patients undergoing percutaneous coronary procedures were collected from patients receiving femoral artery closure by MC (n = 469), Perclose (n = 492), or Angio-Seal (n = 539). Peri-procedural, post-procedural, and post-hospitalization endpoints were: 1) safety of closure method; 2) efficacy of closure method; and 3) patient satisfaction. RESULTS: Patients treated with Angio-Seal experienced shorter times to hemostasis (p < 0.0001, diagnostic and interventional) and ambulation (diagnostic, p = 0.05; interventional, p < 0.0001) than those treated with Perclose. Those treated with Perclose experienced greater access site complications (Perclose vs. Angio-Seal, p = 0.008; Perclose vs. MC, p = 0.06). Patients treated with Angio-Seal reported greater overall satisfaction, better wound healing and lower discomfort (each vs. Perclose or vs. MC, all p < or = 0.0001). For diagnostic cath only, median post-procedural length of stay was reduced by Angio-Seal (Angio-Seal vs. MC, p < 0.0001; Angio-Seal vs. Perclose, p = 0.009). No difference was seen in length of stay for interventional cases. CONCLUSIONS: Overall, Angio-Seal performed better than Perclose or MC in reducing time to ambulation and length of stay among patients undergoing diagnostic procedures. There was a higher rate of successful deployment and shorter time to hemostasis for Angio-Seal, and this was accomplished with no increase in bleeding complications throughout the follow-up. Additionally, Angio-Seal performed better than Perclose in exhibiting a superior 30-day patient satisfaction and patient assessment of wound healing with less discomfort.

Myocardial infarction in the 1990s. Complications, prognosis, and changing patterns of management.

Arrhythmias are the most common complications of acute myocardial infarction. However, other complications, such as ventricular free-wall rupture, thrombosis in locations other than the primary site of infarction, and thromboembolic strokes, also may occur. In addition, thrombolytic therapy given after infarction may cause intracranial hemorrhage, allergic reactions, and hypotension. To reduce the 1-year mortality rate in patients who survive hospitalization, an effort should be made to detect and treat residual ischemia, ventricular dysfunction, and electrical instability. Follow-up rehabilitation and prevention are essential. In this endeavor, primary care physicians, emergency personnel, specialists, nursing staff, and technicians form an integral team.

Myocardial infarction in the 1990s. The importance of early thrombolytic therapy.

Substantial advances in the diagnosis and treatment of ischemic heart disease, especially myocardial infarction, have reduced mortality rates during the past several years. This progress is tempered, however, by the continuing large overall incidence of myocardial infarction and cardiac death in persons in their prime years. Preventive measures are important and are usually best applied by primary care physicians. The acute crisis of coronary artery thrombosis demands accurate diagnosis and timely thrombolytic therapy, which has halved the mortality rate of myocardial infarction. Several effective thrombolytic agents are available; on the basis of several large international trials of these drugs, it appears that the benefits of early and appropriate use of any one of these agents outweigh any individual advantages. In addition to thrombolytics, aspirin and heparin are necessary adjunctive drugs for acute myocardial infarction. Nitroglycerin is helpful, but its essential role seems less evident. Earlier use of beta blockers and angiotensin-converting enzyme inhibitors has been proved effective in reducing mortality. Percutaneous transluminal coronary angioplasty is definitely as effective as thrombolytic therapy, but immediate application is logistically challenging in most US hospitals.

Endomyocardial biopsy.

Endomyocardial biopsy has been used more frequently over the past 10 years in an increasing number of centers in this country and abroad. When done by an experienced physician, it is as safe as routine cardiac catheterization. Although biopsy is not yet applicable in all cases of myocardial disease, many investigators have found this procedure valuable in specific circumstances, including cardiac allograft rejection, anthracycline-induced cardiomyopathy, and myocarditis. With this technique diagnoses can be made for various disorders including cardiac amyloidosis, sarcoidosis, hemochromatosis, and endomyocardial fibrosis. Although helpful in detecting an unsuspected condition or in formulating prognosis in some patients, biopsy is not diagnostically specific in patients with dilated or hypertrophic cardiomyopathy, because these diseases have no completely pathognomonic features under current examination methods. The proper practice of endomyocardial biopsy requires both technical proficiency and expert pathologic interpretation. As a research tool, biopsy will continue to yield new knowledge about myocardial disease and its treatment.

Endomyocardial biopsy.

Endomyocardial biopsy is an accepted, useful invasive tool for the analysis of human endomyocardium at the cellular and subcellular levels. It is applicable in the evaluation of specific diseases including cardiac allograft rejection, myocarditis, anthracycline cardiotoxicity, and infiltrative cardiomyopathies. The procedure can be performed in a cardiac catheterization room on an outpatient basis. The technique is quite safe when performed by trained cardiologists. Left ventricular biopsies are also safe but require systemic heparinization to prevent thromboembolization. The clinical indications for performing an endomyocardial biopsy include routine followup and suspected rejection of cardiac allograft, suspected myocarditis, monitoring or diagnosis of suspected anthracycline cardiotoxicity, and suspected secondary cardiomyopathies. Left ventricular endomyocardial biopsy is indicated for diseases that predominantly involve the left side of the heart, including left heart irradiation, cardiac fibroelastosis in infants, endomyocardial fibrosis, and scleroderma heart disease, and when right ventricular biopsy is unsuccessful. Endomyocardial biopsy is increasingly being used for research in the areas of tissue biochemistry, primary and valvular cardiomyopathies, immunology, beta receptor enzymology, drug interactions, and myocardial fibrosis. Endomyocardial biopsy has not been shown to be clinically useful in the evaluation of primary, dilated, hypertrophic, or alcoholic cardiomyopathies. These disease processes all lack pathognomomic microscopic abnormalities, and subclassification has neither been successful nor therapeutically useful. In addition, this technique is limited in diagnosing any cardiac abnormality that is not diffuse, inasmuch as only a few samples of the endomyocardial layer are obtained for evaluation. Therefore, a negative biopsy result is not 100 percent specific in excluding certain diseases. A further limitation of this technique is the need for an experienced cardiac pathologist who is well versed in interpretation of biopsy specimens. Finally, there should be a sufficiently large case load to train and to maintain skilled practitioners so that the procedure can be performed with little risk. The role of endomyocardial biopsy will continue to expand as research continues to find more uses for the technique and as more clinicians become skilled in its use.

Idiopathic cardiomyopathy, age, and suppressor-cell dysfunction as risk determinants of lymphoma after cardiac transplantation.

A review of lymphomas developing in recipients of cardiac allografts has yielded significant risk factors. Frequency varied strikingly according to original cardiac disease: lymphoma developed in 6 of 37 patients with prior idiopathic cardiomyopathy (I.C.M.) but in one of 54 patients with prior coronary-artery disease (C.A.D.). All patients who developed lymphomas were aged under 40. Combination of both risk factors (I.C.M. and age less than 40) produces a sub-group with a highly significantly increased risk of lymphoma. I.C.M., but not C.A.D., is characterised by a defect in mitogen-induced mononuclear-cell suppressor activity. It is postulated that defective regulation in the immune systems of younger patients under chronic alloantigen stimulation may allow lymphoid proliferation to proceed to lymphoreticular malignancy. Immunosuppressive agents such as azathioprine may exert a co-oncogenic effect.