James E. Dalen

Natural history of pulmonary embolism

It has been found that the proper management of pulmonary embolism improves survival. This article reviews the natural history of pulmonary embolism as it relates to the appropriateness of several alternative therapeutic strategies.

Antithrombotic Therapy in Atrial Fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the American College of Chest Physicians Evidence-Based Guidelines Clinical Practice Guidelines (8th Edition). Grade 1 recommendations indicate that most patients would make the same choice and Grade 2 suggests that individual patients values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppl]:123S-131S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range 2.0-3.0, unless otherwise noted). In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, transient ischemic attack (TIA), or systemic embolism, we recommend long-term anticoagulation with an oral VKA, such as warfarin, because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A). In patients with AF, including those with paroxysmal AF, who have two or more of the risk factors for future ischemic stroke listed immediately below, we recommend long-term anticoagulation with an oral VKA (Grade 1A). Two or more of the following risk factors apply: age >75 years, history of hypertension, diabetes mellitus, moderately or severely impaired left ventricular systolic function and/or heart failure. In patients with AF, including those with paroxysmal AF, with only one of the risk factors listed immediately above, we recommend long-term antithrombotic therapy (Grade 1A), either as anticoagulation with an oral VKA, such as warfarin (Grade 1A), or as aspirin, at a dose of 75-325 mg/d (Grade 1B). In these patients at intermediate risk of ischemic stroke we suggest a VKA rather than aspirin (Grade 2A). In patients with AF, including those with paroxysmal AF, age < or =75 years and with none of the other risk factors listed above, we recommend long-term aspirin therapy at a dose of 75-325 mg/d (Grade 1B), because of their low risk of ischemic stroke. For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C). For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA (Grade 1B). For patients with AF and prosthetic heart valves we recommend long-term anticoagulation with an oral VKA at an intensity appropriate for the specific type of prosthesis (Grade 1B). See CHEST 2008; 133(suppl):593S-629S. For patients with AF of > or =48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA, such as warfarin, for 3 weeks before elective cardioversion and for at least 4 weeks after sinus rhythm has been maintained (Grade 1C). For patients with AF of > or = 48 h or of unknown duration undergoing pharmacological or electrical cardioversion, we also recommend either immediate anticoagulation with unfractionated IV heparin, or low-molecular-weight heparin (LMWH), or at least 5 days of warfarin by the time of cardioversion (achieving an INR of 2.0-3.0) as well as a screening multiplane transesophageal echocardiography (TEE). If no thrombus is seen, cardioversion is successful, and sinus rhythm is maintained, we recommend anticoagulation for at least 4 weeks. If a thrombus is seen on TEE, then cardioversion should be postponed and anticoagulation should be continued indefinitely. We recommend obtaining a repeat TEE before attempting later cardioversion (Grade 1B addressing the equivalence of TEE-guided vs non-TEE-guided cardioversion). For patients with AF of known duration <48 h, we suggest cardioversion without prolonged anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or LMWH at presentation (Grade 2C).

Cardiogenic shock after acute myocardial infarction. Incidence and mortality from a community-wide perspective, 1975 to 1988

BACKGROUND Cardiogenic shock resulting from acute myocardial infarction is a serious complication with a high mortality rate, but little is known about whether its incidence or outcome has changed over time. As part of an ongoing population-based study of acute myocardial infarction, we examined trends over time in the incidence and mortality rate of cardiogenic shock after acute myocardial infarction. METHODS We studied 4762 patients with acute myocardial infarction who were admitted to 16 hospitals in the Worcester, Massachusetts, metropolitan area between 1975 and 1988. We determined the incidence of and short-term and long-term mortality due to cardiogenic shock in each of six years during this study period. RESULTS The incidence of cardiogenic shock complicating acute myocardial infarction remained relatively constant, averaging 7.5 percent. Multivariate regression analysis that controlled for variables affecting incidence revealed significant though inconsistent temporal trends in the incidence of cardiogenic shock. As compared with the risk in 1975, the adjusted relative risk (with 95 percent confidence interval) was 0.83 (0.54 to 1.28) in 1978, 0.96 (0.63 to 1.48) in 1981, 0.68 (0.42 to 1.12) in 1984, 1.16 (0.70 to 1.92) in 1986, and 1.65 (0.99 to 2.77) in 1988. The overall in-hospital mortality rate among patients with cardiogenic shock was significantly higher than that among patients without this complication (77.7 percent vs. 13.5 percent, P less than 0.001). The in-hospital mortality among the patients with shock did not improve between 1975 (73.7 percent) and 1988 (81.7 percent). Long-term survival during the 14-year follow-up period was significantly worse among patients who survived cardiogenic shock during hospitalization than among patients who did not have shock (P less than 0.001). CONCLUSIONS The results of this observational, community-wide study suggest that neither the incidence nor the prognosis of cardiogenic shock resulting from acute myocardial infarction has improved over time. Both in-hospital and long-term survival remain poor for patients with this complication.

Unexplained chest pain in patients with normal coronary arteriograms: a follow-up study of functional status

Approximately 10 per cent of patients referred for coronary arteriography because of chest pain have angiographically normal coronary arteries and no other heart disease. We examined the functional status of 57 patients who had undergone catheterization (23 men and 34 women), all of whom were told that their hearts were normal, that their pain was noncardiac, and that no limitation on activity was necessary. At a mean follow-up time of 16 +/- 7.7 months, 27 of the 57 patients (47 per cent) still described their activity as limited by chest pain (before catheterization, 42 of 57 or 74 per cent); 29 of 57 (51 per cent) were unable to work (before catheterization, 36 of 57 or 63 per cent); and 25 of 57 (44 per cent) still believed that they had heart disease (before catheterization, 45 of 57 or 79 per cent). Use of medical facilities was significantly reduced after catheterization (P < 0.001). At follow-up the physician was more likely than the patient to believe that the symptoms had improved. We conclude that many of these patients remain limited in activity and may benefit from further efforts at comunication and rehabilitation.

A communitywide perspective of sex differences and temporal trends in the incidence and survival rates after acute myocardial infarction and out-of-hospital deaths caused by coronary heart disease.

BackgroundThe purpose of the study was to examine overall differences and temporal trends therein between men and women regarding the incidence rates, in-hospital and long-term survival after initial acute myocardial infarction (AMI), and out-of-hospital deaths caused by coronary disease Methods and ResultsThis nonconcurrent prospective study was carried out in 16 teaching and community hospitals in Worcester, Mass., in six time periods between 1975 and 1988. A total of 3,148 patients hospitalized with validated initial AMI comprised the study sample. The age-adjusted incidence rates of initial AMI increased between 1975 and 1981 in the two sexes, with a marked decrease thereafter, these rates declined by 26% in men and by 22% in women between 1975 and 1988. The overall unadjusted in-hospital case-fatality rates after initial AMI were significantly higher in women (21.7%) than in men (12.7%). Age- and multivariable-adjusted in-hospital case-fatality rates, however, were not significantly different for men compared with women (multivariate-adjusted OR, 0.90; 95% CI, 0.70, 1.16). No clear trends in in-hospital case-fatality rates were observed in men or women over the periods under study. There were no significant sex differences in the age-adjusted long-term survival rates of discharged hospital survivors of AMI. The multivariate-adjusted risk of total mortality among discharged hospital survivors, however, was significantly increased in men (multivariate-adjusted OR, 1.20; 95% CI, 1.03, 1.39); neither of the sexes experienced an improvement over time in long-term prognosis. The incidence rates of out-of-hospital deaths caused by coronary disease declined by 60%o in men and 69%o in women between 1975 and 1988. ConclusionThe results of this multihospital, community-based study suggest declines in the incidence rates of AMI and out-of-hospital deaths caused by coronary disease in men and women over the period under study (1975–1988). No significant sex differences in in-hospital survival were observed, whereas a poorer long-term survival experience after hospital discharge was observed for men compared with women after controlling for potentially confounding prognostic factors. (Circulation 1993;87:1947-1953)

Resolution Rate of Acute Pulmonary Embolism in Man

Abstract In 15 patients with definite angiographic evidence of embolism involving both lungs, and treated with heparin or venous ligation or both, sequential studies showed only minimal angiographic and hemodynamic signs of resolution at seven days. By 10 to 21 days, pressures in the right side of the heart had decreased to near normal levels, and there was unmistakable angiographic evidence of resolution. Complete resolution, with normal angiograms and hemodynamics, was noted in three patients at 14, 15 and 34 days. In other patients angiographic and hemodynamic abnormalities persisted weeks after embolism.

Pulmonary angiography in acute pulmonary embolism: Indications, techniques, and results in 367 patients☆

Abstract Pulmonary angiography is the most specific test available for the diagnosis of acute pulmonary embolism. This technique can safely be performed in critically ill patients. In 367 consecutive studies our incidence of complications has been 4 per cent, and there has been only one death. Hemodynamic studies done as part of the procedure permit evaluation of the severity and the pathophysiology of acute pulmonary embolism. The two diagnostic angiographic findings of pulmonary embolism are intraluminal filling defects and cutoff arteries. Oligemia and asymmetry of blood flow are frequently seen in pulmonary embolism, but are not specific. These latter two abnormalities may occur in chronic lung disease or congestive heart failure without pulmonary embolism. Using these diagnostic criteria in 247 patients studied because of a clinical diagnosis of acute pulmonary embolism, a definitive diagnosis (either definite pulmonary embolism or negative) was established by angiography in 74 per cent. In 9 per cent the diagnosis was probable pulmonary embolism, and in 17 per cent the findings were equivocal for pulmonary embolism. Application of these diagnostic criteria results in minimal false posiive angiographic diagnoses. False negative diagnoses may occur if embolism is limited to peripheral branches of the pulmonary vasculature that are not visualized by current angiographic techniques. The incidence of symptomatic pulmonary embolism limited to these small arteries is uncertain. The primary limitation of this technique is, that in patients with underlying heart disease or chronic lung disease, the results of angiography may be equivocal. The application of new techniques of magnification angiography and/or selective cineangiography offer promise in enhancing the recognition of embolism in this group of patients.

The electrocardiogram in acute pulmonary embolism

Electrocardiograms of 90 patients with arteriographically documented acute submassive or massive pulmonary embolism and no associated cardiac or pulmonary disease were studied. Patients were derived from the Urokinase-Pulmonary Embolism Trial National Cooperative Study. In massive embolism, the electrocardiogram was normal in 6 per cent (3 of 50) of patients. With submassive embolism, 23 per cent of patients (9 of 40) had a normal electrocardiogram. Since one or more of the traditional manifestations of acute cor pulmonale (S1Q3T3, right bundle branch block, P pulmonale, or right axis deviation) occurred in only 26 per cent of patients, one could not rely exclusively upon these electrocardiographic abnormalities for the diagnosis of pulmonary embolism. The most common electrocardiographic abnormalities were nonspecific T wave changes which occurred in 42 per cent of patients and nonspecific abnormalities (elevation or depression) of the RST segment which occurred in 41 per cent of patients. Left axis deviation occurring in 7 per cent of the patients was as frequent as right axis deviation. Low voltage QRS complexes, previously undescribed in pulmonary embolism, occurred in 6 per cent of patients. None of the patients had atrial flutter or atrial fibrillation, which appears to occur more typically in patients with pulmonary embolism who have preexistent cardiac disease. All of the varieties of electrocardiographic abnormalities disappeared in some of the patients by 2 wk. Inversion of the T wave was the most persistent abnormality. Larger defects on the lung scan or pulmonary arteriogram occurred in patients with various abnormalities on the electrocardiogram than in patients with normal electrocardiograms. The pulmonary arterial mean pressure and/or right ventricular end-diastolic pressure was significantly higher in patients with several varieties of abnormal electrocardiograms, although the partial pressure of oxygen in arterial blood, in general, did not differ from that in patients with normal electrocardiograms. These hemodynamic correlations, made for the first time in patients, suggest that acute ventricular dilatation, possibly in combination with hypoxemia, is a causative factor of the electrocardiographic changes in acute massive or submassive pulmonary embolism.

Six- and twelve-month follow-up of the Phase I Thrombolysis in Myocardial Infarction (TIMI) trial

The Thrombolysis in Myocardial Infarction (TIMI) trial Phase I was designed to compare the efficacy and side effects of intravenous recombinant tissue-type plasminogen activator (rt-PA) and intravenous streptokinase (SK) in patients with acute myocardial infarction (AMI). As previously reported, rt-PA led to a reperfusion rate of 62% of totally occluded coronary arteries compared with 31% for SK (p less than 0.001). This study was not designed to determine if intravenous thrombolytic therapy decreases the mortality of AMI; however, the findings in these patients after 1 year of follow-up do permit certain insights into the impact of early reperfusion and reocclusion on the clinical course of patients with AMI. The mortality rate at 6 and 12 months was not significantly different in patients treated with rt-PA compared with SK (7.7% and 10.5% rt-PA vs 9.5% and 11.6% for SK). The frequency of recurrent AMI, coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) was similar in the 2 treatment groups. There was no significant difference in 6- and 12-month mortality or in the rate of recurrent AMI in patients who received thrombolytic therapy before compared with after 4 hours of the onset of AMI symptoms. When the results were analyzed on the basis of the patency of the infarct-related artery, irrespective of thrombolytic agent used, for those patients with patent arteries 90 minutes after the initiation of therapy, there was a trend toward a lower 6-month (5.6% vs 12.5%) and 12-month mortality (8.1% vs 14.8%) (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence and case fatality rates of acute myocardial infarction (1975–1984): The Worcester Heart Attack Study

During the calendar years 1975, 1978, 1981, and 1984, a community-wide study in the Worcester, Massachusetts, metropolitan area has examined time trends in the attack and case fatality rates of acute myocardial infarction (MI) as well as the occurrence of out-of-hospital coronary heart disease deaths. Between 1975 and 1981, there was a slight increase in the age-adjusted attack rates of acute MI; between 1981 and 1984, however, there was a dramatic decline in the incidence rates of acute MI. These temporal trends over the 10-year period examined resulted in an overall decrease in both the incidence rates of initial (255 per 100,000-1975; 186 per 100,000-1984) as well as recurrent (133 per 100,000-1975; 104 per 100,000-1984) acute MI in the 16 hospitals surveyed. The age-adjusted in-hospital case fatality rates of acute MI declined consistently over the periods studied, from 22.2% in 1975 to 20.3% in 1978, 17.8% in 1981, and to 15.1% in 1984, for an overall decline of 32% over the 10-year period studied. No significant differences, however, were seen in the long-term survival rates of patients discharged from the hospital after acute MI in either 1975, 1978, 1981, or 1984. A consistent decline was seen in the age-adjusted mortality rates (per 100,000) of out-of-hospital coronary heart disease between 1975 (265), 1978 (174), 1981 (170), and 1984 (148).(ABSTRACT TRUNCATED AT 250 WORDS)