Annette Geibel

Management Strategies and Determinants of Outcome in Acute Major Pulmonary Embolism: Results of a Multicenter Registry ☆

OBJECTIVES The present study investigated current management strategies as well as the clinical course of acute major pulmonary embolism. BACKGROUND The clinical outcome of patients with acute pulmonary embolism who present with overt or impending right heart failure has not yet been adequately elucidated. METHODS The 204 participating centers enrolled a total of 1,001 consecutive patients. The inclusion criteria were based on the clinical findings at presentation and the results of electrocardiographic, echocardiographic, nuclear imaging and cardiac catheterization studies. RESULTS Echocardiography was the most frequently performed diagnostic procedure (74%). Lung scan or pulmonary angiography were performed in 79% of clinically stable patients but much less frequently in those with circulatory collapse at presentation (32%, p < 0.001). Thrombolytic agents were given to 478 patients (48%), often despite the presence of contraindications (193 [40%] of 478). The frequency of initial thrombolysis was significantly higher in clinically unstable than in normotensive patients (57% vs. 22%, p < 0.001). Overall in-hospital mortality rate ranged from 8.1% in the group of stable patients to 25% in those presenting with cardiogenic shock and to 65% in patients necessitating cardiopulmonary resuscitation. Major bleeding was reported in 92 patients (9.2%), but cerebral bleeding was uncommon (0.5%). Finally, recurrent pulmonary embolism occurred in 172 patients (17%). CONCLUSIONS Current management strategies of acute major pulmonary embolism are largely dependent on the degree of hemodynamic instability at presentation. In the presence of severe hemodynamic compromise, physicians often rely on the findings of bedside echocardiography and proceed to thrombolytic treatment without seeking further diagnostic certainty in nuclear imaging or angiographic studies.

Right Ventricular Infarction as an Independent Predictor of Prognosis after Acute Inferior Myocardial Infarction

BACKGROUND Acute inferior myocardial infarction frequently involves the right ventricle. We hypothesized that right ventricular involvement, as diagnosed by ST-segment elevation in the right precordial lead V4R, may affect the prognosis of patients with inferior myocardial infarctions. METHODS In 200 consecutive patients admitted to the hospital with acute inferior myocardial infarctions, we assessed the prevalence and diagnostic accuracy of ST-segment elevation in lead V4R (as compared with four other diagnostic procedures) to identify right ventricular involvement and its prognostic implications for in-hospital and long-term outcomes. RESULTS The in-hospital mortality after inferior myocardial infarction was 19 percent, and major complications occurred in 47 percent of the patients. The presence of ST-segment elevation in lead V4R in 107 patients (54 percent) was highly predictive of right ventricular infarction (sensitivity, 88 percent; specificity, 78 percent; diagnostic accuracy, 83 percent), as compared with the other diagnostic procedures. The patients with ST-segment elevation in lead V4R had a higher in-hospital mortality rate (31 percent vs. 6 percent, P < 0.001) and a higher incidence of major in-hospital complications (64 percent vs. 28 percent, P < 0.001) than did those without ST-elevation in V4R. Multiple logistic-regression analysis showed ST elevation in V4R to be independent of and superior to all other clinical variables available on admission for the prediction of in-hospital mortality (relative risk, 7.7; 95 percent confidence interval, 2.6 to 23) and major complications (relative risk, 4.7; 95 percent confidence interval, 2.4 to 9). The post-hospital course (follow-up, at least 1 year; mean follow-up, 37 months) was similar in patients with and in those without electrocardiographic evidence of right ventricular infarction. CONCLUSIONS Right ventricular involvement during acute inferior myocardial infarction can be accurately diagnosed by the presence of ST-segment elevation in lead V4R, a finding that is a strong, independent predictor of major complications and in-hospital mortality. Electrocardiographic assessment of right ventricular infarction should be routinely performed in all patients with acute inferior myocardial infarctions.

Fibrinolysis for patients with intermediate-risk pulmonary embolism

BACKGROUND The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial. METHODS In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization. RESULTS Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42). CONCLUSIONS In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).

Association Between Thrombolytic Treatment and the Prognosis of Hemodynamically Stable Patients With Major Pulmonary Embolism Results of a Multicenter Registry

BACKGROUND Thrombolytic treatment has been shown to accelerate resolution of major pulmonary embolism and lead to a rapid improvement of right-side hemodynamics. However, the association between these favorable effects and the clinical outcome of patients who have no severe hemodynamic compromise at presentation remains unknown. METHODS AND RESULTS The present multicenter registry included 719 consecutive patients with major pulmonary embolism according to clinical, echocardiographic, scintigraphic, and cardiac catheterization criteria. Symptom onset was acute (<48 hours) in 63% of patients. All patients were hemodynamically stable (ie, without evidence of cardiogenic shock) at presentation. Primary thrombolytic treatment (within 24 hours of diagnosis) was given to 169 patients (23.5%), whereas the remaining 550 patients were initially treated with heparin alone. Overall 30-day mortality was significantly lower in the patients who received thrombolytic agents (4.7 versus 11.1%, P=.016). Clinical factors associated with a higher death rate were syncope (P=.012), arterial hypotension (P=.021), history of congestive heart failure (P=.013), and chronic pulmonary disease (P=.032). However, only primary thrombolysis was found by multivariate analysis to be an independent predictor of survival (odds ratio for in-hospital death, 0.46; 95% confidence interval, 0.21 to 1.00). Patients who underwent early thrombolytic treatment had a reduced rate of recurrent pulmonary embolism (7.7 versus 18.7%, P<.001) but also a higher frequency of major bleeding episodes (21.9% versus 7.8%, P<.001). Cerebral bleeding occurred in 2 patients in each treatment group, and 1 patient in each group died of a bleeding complication. CONCLUSIONS The results of our study suggest that thrombolysis may favorably affect the clinical outcome of hemodynamically stable patients with major pulmonary embolism.

A Comparison of Surgical and Medical Therapy for Atrial Septal Defect in Adults

BACKGROUND The surgical closure of an atrial septal defect is frequently recommended for patients over 40 years of age. However, the prognosis for such patients with unrepaired defects is largely unknown, and the outcome for patients operated on after the fourth decade of life has not yet been compared with that for medically treated patients in a controlled follow-up study. METHODS In a retrospective study, we examined the clinical course of 179 consecutive patients with isolated atrial septal defects diagnosed after the age of 40. The 84 patients (47 percent) who underwent surgical repair were compared with the 95 patients (53 percent) who were treated medically. The mean (+/-SD) follow-up period was 8.9 +/- 5.2 years (range, 1 to 26). RESULTS Multivariate analysis revealed that surgical closure of the defect significantly reduced mortality from all causes (relative risk, 0.31; 95 percent confidence interval, 0.11 to 0.85). The adjusted 10-year survival rate of surgically treated patients was 95 percent, as compared with 84 percent for the medically treated patients. In addition, surgical treatment prevented functional deterioration, as measured by the New York Heart Association class (relative risk, 0.21; 95 percent confidence interval, 0.08 to 0.55). However, the incidence of new atrial arrhythmias or of cerebrovascular insults in the two groups was not significantly different. CONCLUSIONS The surgical repair of an atrial septal defect in patients over 40 years of age, as compared with medical therapy, increases long-term survival and limits the deterioration of function due to heart failure. However, surgically treated patients should be followed closely for the onset of atrial arrhythmias so as to reduce the risk of thromboembolic complications.

Patent Foramen Ovale Is an Important Predictor of Adverse Outcome in Patients With Major Pulmonary Embolism

BACKGROUND Right-to-left shunt through a patent foramen ovale is frequently diagnosed by contrast echocardiography and can be particularly prominent in the presence of elevated pressures in the right side of the heart. Its prognostic significance in patients with pulmonary thromboembolism, however, is unknown. METHODS AND RESULTS The present prospective study included 139 consecutive patients with major pulmonary embolism diagnosed on the basis of clinical, echocardiographic, and cardiac catheterization criteria. All patients underwent contrast echocardiography at presentation. The end points of the study were overall mortality and complicated clinical course during the hospital stay defined as death, cerebral or peripheral arterial thromboembolism, major bleeding, or need for endotracheal intubation or cardiopulmonary resuscitation. Patent foramen ovale was diagnosed in 48 patients (35%). These patients had a death rate of 33% as opposed to 14% in patients with a negative echo-contrast examination (P=.015). Logistic regression analysis demonstrated that the only independent predictors of mortality in the study population were a patent foramen ovale (odds ratio [OR], 11.4; P<.001) and arterial hypotension at presentation (OR, 26.3; P<.001). Patients with a patent foramen ovale also had a significantly higher incidence of ischemic stroke (13% versus 2.2%; P=.02) and peripheral arterial embolism (15 versus 0%; P<.001). Overall, the risk of a complicated in-hospital course was 5.2 times higher in this patient group (P<.001). CONCLUSIONS In patients with major pulmonary embolism, echocardiographic detection of a patent foramen ovale signifies a particularly high risk of death and arterial thromboembolic complications.

N-Terminal Pro–Brain Natriuretic Peptide or Troponin Testing Followed by Echocardiography for Risk Stratification of Acute Pulmonary Embolism

Background—Brain natriuretic peptide (BNP) and N-terminal (NT)-proBNP have recently emerged as promising parameters for risk assessment in acute pulmonary embolism (PE). However, their positive predictive value is low, and the prognostic implications of NT-proBNP or troponin elevation alone are questionable. Methods and Results—To determine whether the combination of NT-proBNP testing with echocardiography may identify both low-risk and high-risk patients with PE, we examined 124 consecutive patients with proved PE. All underwent echocardiography on admission to detect right ventricular dysfunction. NT-proBNP and troponin concentrations were measured in one core laboratory. The primary end point was death or major in-hospital complications. The cutoff level of 1000 pg/mL had a high negative predictive value (95% for a complicated course, 100% for death), but NT-proBNP ≥1000 pg/mL did not independently predict an adverse outcome. Combination of NT-proBNP testing with echocardiography identified 3 major risk groups. A positive echocardiogram was associated with a 12-fold elevation in complication risk compared with patients with low NT-proBNP (P=0.002), whereas NT-proBNP elevation without right ventricular dysfunction on echocardiography only slightly increased the risk of an adverse outcome (P=0.17). The combination of cardiac troponin testing with echocardiography yielded similar complication rates in the lowest-risk group and a similar magnitude of risk elevation for the highest-risk patients, but it also increased the number of intermediate-risk groups. Conclusions—Our results support a simple risk stratification algorithm for patients with PE, with the use of NT-proBNP or troponin testing as an initial step that should be followed by echocardiography if elevated levels of the biomarker are found.

Mode of death in idiopathic dilated cardiomyopathy: A multivariate analysis of prognostic determinants

A total of 110 patients with idiopathic dilated cardiomyopathy were followed prospectively for 53 +/- 8 (range 41 to 69) months to determine prognostic factors identifying patients at risk for sudden death or death from congestive heart failure. During the follow-up period 39 patients died, 14 of congestive heart failure and 25 suddenly. The incidence of cardiac death after 1 year was 18%, after 2 years 35%, and after 4 years 39%. Multivariate logistic regression analysis identified four independent prognostic factors: left ventricular ejection fraction, cardiac index, number of ventricular pairs/24 hours, and atrial rhythm (sinus rhythm or atrial fibrillation). With the final model of logistic regression 77 of 88 patients (88%) could be classified correctly as being at risk for death from chronic heart failure or sudden cardiac death. Patients who were likely to die of congestive heart failure were characterized by a markedly impaired left ventricular function (measured in terms of left ventricular ejection fraction, cardiac index, or both) and a low number of pairs/24 hours. The association between frequent complex ventricular arrhythmias and depressed left ventricular function identifies patients who are at risk for sudden death. The presence of atrial fibrillation significantly increases the risk of sudden death and death from congestive heart failure.

Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: A prospective, randomized study

This study compares inducibility of ventricular tachyarrhythmias by programmed electrical stimulation of the heart in patients with myocardial infarction with and without reperfusion after streptokinase therapy. Sixty-two consecutive patients admitted with an acute myocardial infarction were randomized to either combined intravenous and intracoronary streptokinase (streptokinase group) or to standard coronary care unit treatment (control group). Thirty-six of the 62 patients (21 patients from the streptokinase and 15 from the control group) with a first myocardial infarction were studied by programmed ventricular stimulation after a mean of 26 +/- 14 days. No patient had a history of antiarrhythmic drug use or documentation of a ventricular arrhythmia before the initial admission. A sustained ventricular arrhythmia was induced in 10 (48%) of the 21 patients randomized to streptokinase therapy and in all 15 (100%) control patients (p less than 0.001). Sustained monomorphic ventricular tachycardia was induced in 6 (29%) and 10 (67%) patients, respectively (p less than 0.05). To terminate an induced arrhythmia, direct current countershock was required in 33% of patients in the streptokinase group and 73% of patients in the control group (p less than 0.02). Seventeen of the 21 patients treated with streptokinase and no control patient had evidence of early reperfusion 200 +/- 70 minutes after the onset of pain. In comparison with patients without early reperfusion, patients in the reperfused group had a lower maximal serum creatine kinase value (p less than 0.01), a shorter time to peak creatine kinase value (p less than 0.001) and a higher angiographic left ventricular ejection fraction (62 versus 45%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Determinants of prognosis in idiopathic dilated cardiomyopathy as determined by programmed electrical stimulation.

The incidence and prognostic significance of electrically induced ventricular arrhythmias were prospectively assessed in 42 patients with idiopathic dilated cardiomyopathy. All patients underwent 24-hour, long-term electrocardiographic (Holter) monitoring and 30 were analyzed by a signal-averaging vectorcardiographic procedure at entry into the study. Their response to programmed electrical stimulation during basic right ventricular pacing was investigated using 1 and 2 ventricular extrastimuli. A monomorphic tachycardia was not induced in any patient. In 36 patients (86%) polymorphic ventricular arrhythmias were initiated. Three or more induced consecutive ventricular premature complexes occurred in 9 patients (21%), nonsustained polymorphic ventricular tachycardia in 2 (4.8%) and ventricular fibrillation in 1 patient (2.4%). There was no association between electrically induced polymorphic ventricular arrhythmias and the degree of impairment of left ventricular function. Furthermore, the incidence of induced ventricular arrhythmias was not related to the Lown grade or to the total number of ventricular premature complexes during Holter monitoring. A late potential was detected by the averaged vectorcardiogram in only 1 of the 30 patients. During follow-up (mean 16 +/- 7 months) 7 patients died, 5 from chronic congestive heart failure and 2 from sudden cardiac death. No patient had an electrically induced arrhythmia of 3 or more ventricular premature complexes.(ABSTRACT TRUNCATED AT 250 WORDS)