The New England Journal of Medicine

Echt, Debra S.; Liebson, Philip R.; Mitchell, L. Brent; Peters, Robert W.; Obias-Manno, Dulce; Barker, Allan H.; Arensberg, Daniel; Baker, Andrea; Friedman, Lawrence; Greene, H. Leon; Huther, Melissa L.; Richardson, David W.; ,

doi: 10.1056/NEJM199103213241201pmid: 1900101

AbstractBackground and Methods.In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo.Results.Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty.Conclusions.There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown. (N Engl J Med 1991; 324:781–8.)

Chapman, Kenneth R.; Verbeek, P. Richard; White, John G.; Rebuck, Anthony S.

doi: 10.1056/NEJM199103213241202pmid: 1997850

AbstractBackground.Relapse after the treatment of acute asthma in the emergency room is common (occurring in 25 to 30 percent of cases) and is not accurately predicted by any available measurements. We studied the usefulness of prednisone in reducing this high rate of relapse.Methods.One hundred twenty-two patients treated in the emergency room for acute exacerbations of asthma were assigned in a randomized, double-blind fashion to receive at discharge either prednisone for eight days (the dose being tapered from 40 to 0 mg per day) or matching placebo. Ninety-three were subsequently discharged from the emergency room and participated in the trial. On days 1, 7, and 14 after discharge, the patients were assessed during home visits with spirometry and diary-card review; they were contacted by telephone on day 21. Relapse was defined as an unscheduled medical visit occasioned by the patient's perceived need for further asthma treatment.Results.The overall risk of relapse was significantly lower in the prednisone group (P<0.05), with a significantly reduced rate of relapse during the first 10 days of follow-up (3 of 48, as compared with 11 of 45 in the placebo group; P<0.05). Thereafter (days 11 though 21), there was no further significant difference in relapse rates between treatment groups (five in the prednisone group and six in the placebo group). During the first week after discharge, patients receiving prednisone reported significantly lower mean (±SD) daily symptom scores for shortness of breath (1.4±0.4 vs. 2.5±0.4, P<0.01 ) and less frequent use of an inhaled bronchodilator (5.2±0.5 vs. 6.9±0.2 puffs per day, P<0.05) than patients receiving placebo. Subsequently, symptom scores and bronchodilator use were similar in the two groups.Conclusions.A short course of prednisone reduced early relapse rates after the treatment of acute asthma in the emergency room, an effect limited to the period of steroid administration. (N Engl J Med 1991; 324: 788–94.)

Daniel, Werner G.; Mügge, Andreas; Martin, Randolph P.; Lindert, Oliver; Hausmann, Dirk; Nonnast-Daniel, Barbara; Laas, Joachim; Lichtlen, Paul R.

doi: 10.1056/NEJM199103213241203pmid: 1997851

AbstractBackground.Echocardiography is recognized as the method of choice for the noninvasive detection of valvular vegetations in patients with infective endocarditis, with transesophageal echocardiography being more accurate than transthoracic echocardiography. The diagnosis of associated abscesses by transthoracic echocardiography is difficult or even impossible in many cases, however, and it is not known whether transesophageal echocardiography is any better.Methods.To determine the value of transesophageal echocardiography in the detection of abscesses associated with endocarditis, we studied prospectively by two-dimensional transthoracic and transesophageal echocardiography 118 consecutive patients with infective endocarditis of 137 native or prosthetic valves that was documented during surgery or at autopsy.Results.During surgery or at autopsy, 44 patients (37.3 percent) had a total of 46 definite regions of abscess. Abscesses were more frequent in aortic-valve endocarditis than in infections of other valves, and the infecting organism was more often staphylococcus (52.3 percent of cases) in patients with abscesses than in those without abscesses (16.2 percent). The hospital mortality rate was 22.7 percent in patients with abscesses, as compared with 13.5 percent in patients without abscesses. Whereas transthoracic echocardiography identified only 13 of the 46 areas of abscess, the transesophageal approach allowed the detection of 40 regions (P<0.001). Sensitivity and specificity for the detection of abscesses associated with endocarditis were 28.3 and 98.6 percent, respectively, for transthoracic echocardiography and 87.0 and 94.6 percent for transesophageal echocardiography; positive and negative predictive values were 92.9 and 68.9 percent, respectively, for the transthoracic approach and 90.9 and 92.1 percent for the transesophageal approach. Variation between observers was 3.4 percent for transthoracic and 4.2 percent for transesophageal echocardiography.Conclusions.The data indicate that transesophageal echocardiography leads to a significant improvement in the diagnosis of abscesses associated with endocarditis. The technique facilitates the identification of patients with endocarditis who have an increased risk of death and permits earlier treatment. (N Engl J Med 1991; 324:795–800.)

Wiersma, Susan R.; Ortega, Jorge; Sobel, Eugene; Weinberg, Kenneth I.

doi: 10.1056/NEJM199103213241204pmid: 1997852

AbstractBackground.Leukemic cells in 15 to 25 percent of patients with acute lymphoblastic leukemia (ALL) express myeloid antigens as well as lymphoid antigens (the latter reflecting B-cell or T-cell lineage). The relations of myeloid-antigen expression to other features of ALL and to prognosis have been controversial.Methods.We analyzed clinical and laboratory features present at diagnosis in 236 consecutive cases of ALL in children. Immunophenotyping, including single- and dual-fluorescence analyses, was used to classify leukemic cells as B or T lymphoblasts and also to identify myeloid-antigen expression — the simultaneous expression of lymphoid-associated antigens and at least one of three myeloid-associated antigens (CD33, CD13, and CD14) on cells classified as L1 or L2 according to the French—American—British system.Results.Forty-five of 185 patients with B-lineage ALL had myeloid-antigen expression, as did 8 of 41 patients with T-lineage ALL. In 10 patients, the lineage could not be determined. Myeloid-antigen expression was associated with L2 morphology (P<0.05), but it did not correlate with other prognostic features recognized previously. Multivariate analysis showed that myeloid-antigen expression was an important predictor of relapse in childhood ALL and the most significant prognostic factor statistically (P<0.0001). A white-cell count ≥50×109 per liter at diagnosis was also an important and highly significant prognostic feature (P<0.001). After 40 months, the estimated disease-free survival for patients with ALL was 84 percent for those without myeloid-antigen expression and with a low white-cell count, 57 percent for those without myeloid-antigen expression and with a high white-cell count, 47 percent for those with myeloid-antigen expression and a low white-cell count, and 26 percent for those with myeloid-antigen expression and a high white-cell count (P<0.00001).Conclusions.Myeloid-antigen expression is an important independent predictor of a poor response to chemotherapy in childhood ALL. (N Engl J Med 1991; 324: 800–8.)

Lipshultz, Steven E.; Colan, Steven D.; Gelber, Richard D.; Perez-Atayde, Antonio R.; Sallan, Stephen E.; Sanders, Stephen P.

doi: 10.1056/NEJM199103213241205pmid: 1997853

AbstractBackground.Cardiotoxicity is a recognized complication of doxorubicin therapy, but the long-term effects of doxorubicin are not well documented. We therefore assessed the cardiac status of 115 children who had been treated for acute lymphoblastic leukemia with doxorubicin 1 to 15 years earlier in whom the disease was in continuous remission.Methods.Eighteen patients received one dose of doxorubicin (45 mg per square meter of body-surface area), and 97 received multiple doses totaling 228 to 550 mg per square meter (median, 360). The median interval between the end of treatment and the cardiac evaluation was 6.4 years. Our evaluation consisted of a history, 24-hour ambulatory electrocardiographic recording, exercise testing, and echocardiography.Results.Fifty-seven percent of the patients had abnormalities of left ventricular afterload (measured as end-systolic wall stress) or contractility (measured as the stress—velocity index). The cumulative dose of doxorubicin was the most significant predictor of abnormal cardiac function (P<0.002). Seventeen percent of patients who received one dose of doxorubicin had slightly elevated age-adjusted afterload, and none had decreased contractility. In contrast, 65 percent of patients who received at least 228 mg of doxorubicin per square meter had increased afterload (59 percent of patients), decreased contractility (23 percent), or both. Increased afterload was due to reduced ventricular wall thickness, not to hypertension or ventricular dilatation. In multivariate analyses restricted to patients who received at least 228 mg of doxorubicin per square meter, the only significant predictive factors were a higher cumulative dose (P = 0.01), which predicted decreased contractility, and an age of less than four years at treatment (P = 0.003), which predicted increased afterload. Afterload increased progressively in 24 of 34 patients evaluated serially (71 percent). Reported symptoms correlated poorly with indexes of exercise tolerance or ventricular function. Eleven patients had congestive heart failure within one year of treatment with doxorubicin; five of them had recurrent heart failure 3.7 to 10.3 years after completing doxorubicin treatment, and two required heart transplantation. No patient had late heart failure as a new event.Conclusions.Doxorubicin therapy in childhood impairs myocardial growth in a dose-related fashion and results in a progressive increase in left ventricular afterload, sometimes accompanied by reduced contractility. We hypothesize that the loss of myocytes during doxorubicin therapy in childhood might result in inadequate left ventricular mass and clinically important heart disease in later years. (N Engl J Med 1991; 324:808–15.)

Waeckerle, Joseph F.

doi: 10.1056/NEJM199103213241206pmid: 1997854

Disasters are tragedies that overwhelm our communities, destroy our property, and harm our populations. The United Nations General Assembly, recognizing the magnitude of the problem, has declared the 1990s the International Decade of Natural Disaster Reduction and has called for a worldwide effort to reduce the loss of life and property. The involvement of the medical community in this effort is crucial. Disasters are the results of natural or man-made events and are routinely described in terms of certain characteristics (Table 1).1 2 3 Yet each is unique, each is of extreme urgency, and each places a tremendous burden on the community . . .

Klibanski, Anne; Zervas, Nicholas T.

doi: 10.1056/NEJM199103213241207pmid: 1997855

DIAGNOSTIC, medical, and surgical advances over the past decade have greatly changed the management of secretory pituitary tumors. Improvements in magnetic resonance imaging have advanced the noninvasive visualization of smaller pituitary adenomas. Enhancement with gadolinium discloses the three-dimensional anatomy of most tumors and permits a precise assessment of their location, their volume, and the involvement of the carotid arteries, optic nerves, and chiasm. It is also possible to determine more confidently whether a tumor is fibrous or cystic and whether it has undergone necrosis or hemorrhage. The advent of bilateral sampling of the petrosal sinus for corticotropin coupled with advances . . .

Faxon, David P.; O'Gara, Patrick T.

doi: 10.1056/NEJM199103213241208pmid: 1997856

Presentation of Case A 67-year-old man was admitted to the hospital because of a ventricular septal defect and increasing exertional dyspnea. There was a history of a heart murmur since childhood. Thirty years before admission the patient received a diagnosis of a ventricular septal defect in consultation with Dr. Paul Dudley White. Twenty-five years before entry he was admitted to this hospital for treatment of subacute bacterial endocarditis that was caused by a coagulase-negative staphylococcal species. Three years later he was treated elsewhere for what was believed to be congestive heart failure. Digoxin was begun, and diuretic medications were administered . . .

Pearlman, Alan S.

doi: 10.1056/NEJM199103213241209pmid: 1997857

Over the past 30 years, cardiac ultrasound examinations have been used in an ever-increasing number of clinical applications. Echocardiography currently has important uses in a range of disorders, including valvular, ischemic, myocardial, pericardial, congenital, infectious, and neoplastic diseases.1 To an important extent, this development has been made possible by a sequence of new diagnostic methods arising from technological innovations. From early time—motion studies, echocardiography now has evolved to include two-dimensional imaging, spectral Doppler measurement of blood-flow velocity with pulsed-wave and continuous-wave techniques, color Doppler flow imaging, contrast echocardiography, and stress echocardiography. The latest method is transesophageal echocardiography. In simple terms, . . .

Doroshow, James H.

doi: 10.1056/NEJM199103213241210pmid: 1997858

Doxorubicin (Adriamycin) and the related anthracycline antibiotic daunorubicin play a central part in cancer therapy because of their efficacy in the treatment of hematologic cancers (both acute leukemias and lymphomas), as well as carcinomas of the breast, lung, and thyroid and bone and soft-tissue sarcomas.1 Furthermore, these drugs are widely used in both adults and children in treatment regimens aimed at the cure of neoplasms as well as at palliation. The discovery more than 20 years ago that therapy with anthracyclines could produce irreversible and possibly life-threatening cardiac injury has led to limitations on the use of these drugs in . . .