Prognostic Value of ECG Among Patients with Acute Pulmonary Embolism and Normal Blood Pressure

Objective

To investigate the prognostic value of electrocardiography (ECG) alone or in combination with echocardiography in patients with acute pulmonary embolism and normal blood pressure.

Methods

Consecutive adult patients presenting to the emergency department at Azienda Ospedaliero-Universitaria Careggi with the first episode of pulmonary embolism were included. Patients with systolic blood pressure less than 100 mm Hg were excluded. ECG and echocardiography were performed within 1 hour from diagnosis and evaluated in a blinded fashion. Right ventricular strain was diagnosed in the presence of one or more of the following ECG findings: complete or incomplete right ventricular branch block, S1Q3T3, and negative T wave in V1-V4. The main outcome measurement was clinical deterioration or death during in-hospital stay. The association of variables with the main outcome was evaluated by multivariate Cox survival analysis.

Results

A total of 386 patients with proved pulmonary embolism were included in the study; 201 patients (52%) had right ventricular dysfunction according to echocardiography, and 130 patients (34%) showed right ventricular strain. Twenty-three patients (6%) had clinical deterioration or died. At multivariate survival analysis, right ventricular strain was associated with adverse outcome (hazard ratio 2.58; 95% confidence interval, 1.05-6.36) independently of echocardiographic findings. Patients with both right ventricular strain and right ventricular dysfunction (26%) showed an 8-fold elevated risk of adverse outcome (hazard ratio 8.47; 95% confidence interval, 2.43-29.47).

Conclusion

Right ventricular strain pattern on ECG is associated with adverse short-term outcome and adds incremental prognostic value to echocardiographic evidence of right ventricular dysfunction in patients with acute pulmonary embolism and normal blood pressure.     

肺栓塞患者心电图ST段压低与严重临床事件关系的临床研究

目的:通过观察44例肺栓塞患者心电图ST段的变化,探讨肺栓塞患者心电图ST段压低与心肌损伤以及严重临床事件发生的关系.方法:对44例患者进行前瞻性研究.根据心电图ST段变化,将患者分为两组:ST段压低组(23例)和非ST段压低组(21例).同时均于24 h内相隔8～12 h两次采血测定血清肌钙蛋白I(TnI),两次都出现阳性结果,即为TnI阳性.观察住院期间两组患者的临床表现,对严重临床事件及死亡情况进行统计.结果:44例肺栓塞患者心电图ST段压低见于Ⅱ、Ⅲ、aVF、V_(1～4)导联.两组中共有12例Tnl阳性,其中ST段压低组11例,非ST段压低组1例,两组相比P=0.0014;共有13例次发生严重临床事件,其中ST段压低组11例次,非ST段压低组2例次,两组相比P=0.0054;死亡病例6例,ST段压低组5例,非ST段压低组1例,两组相比P=0.0209.结论:肺栓塞患者心电图ST段压低提示心肌受损及严重临床事件的发生率较高.     

High rate of positive lymph nodes in T1a gallbladder cancer does not translate to decreased survival: a population-based,propensity score adjusted analysis

Background

Current consensus guidelines suggest that gallbladder cancer (GBC) patients with resected T1a disease can be observed while patients with T1b or greater lesions should undergo lymphadenectomy (LNE). The primary aim of this study was to critically explore the impact of LNE in early-stage GBC on overall survival (OS) on a population-based level.

Morphologic and functional substrate of thyrotoxicosis caused by nodular goiters

The pathogenesis of nonimmunogenic thyrotoxicosis caused by nodular goiters—with the exception of true toxic adenoma—was investigated in 11 patients by means of scintigraphic, morphologic and autoradiographic technics. The basic event is the appearance, for unknown reasons, of autonomously functioning follicles which are morphologically indistinguishable from normal follicles. Four basic patterns of intrathyroidal distribution of autonomously functioning follicles are individualized: Type I = multiple individual autonomously functioning follicles scattered throughout the goiter. Type II = clustered autonomous follicles without demarcation from less active parenchyma. Type III = multiple microadenomas. Type IV = autonomous function of the majority of all follicles. In all four types, the autonomous follicles occur without recognizable relation to nodule boundaries. Scintiscans cannot predict the microstructure of these types of goiters. More than one pattern of distribution of autonomously functioning follicles may occur within a single goiter.The growth of thyroid nodules is independent of, and certainly not a prerequisite to, thyrotoxicosis. Rather, the appearance of thyrotoxicosis in this type of multinodular goiter depends on (1) the number of autonomous follicles throughout the gland and (2) their mean hormone-producing capacity per unit of time.     

Cardiovascular and endocrine profile of adrenergic neurone blockade in normal and hypertensive man.

Some cardiovascular and endocrine effects of adrenergic blockade were assessed in six normal subjects, six patients with mild hypertension (diastolic pressure < 100 mm Hg) and six patients with moderate to severe essential hypertension. Administration of the inhibitory agent, debrisoquine, for six weeks markedly decreased supine and upright plasma norepinephrine levels, and norepinephrine excretion in all three groups. Supine and upright blood pressure was decreased more (p < 0.001) in those with moderate to severe hypertension (15 and 27 per cent) than in those with mild hypertension (6 and 8 per cent) and remained unchanged in normal subjects. Pulse rate and plasma renin levels were lowered (p <0.01) in patients with moderate to severe hypertension, but not in normal or mildly hypertensive subjects. The different influence of blood pressure, pulse rate and renin in the three groups could not be explained by variations in drug dosage, norepinephrine inhibition, age, basal sodium balance or secondary blood volume expansion, the latter being marked in all groups. Diuretic therapy in addition to sympathetic inhibition reversed blood volume expansion, and further augmented the reduction in supine and upright blood pressure in patients with moderate to severe (?21 and ?47 per cent) or mild hypertension (?8 and ?12 per cent). Plasma aldosterone, cortisol and epinephrine values remained unchanged, and no severe or intolerable side effects occurred during treatment. These data suggest that adrenergic neuron blockade with modest doses of debrisoquine, combined with a diuretic, may be an effective and acceptable mode of therapy in patients with either mild or more severe hypertension. The hypotensive, cardiac-slowing and renin-inhibitory potential of adrenergic neuron blockade may be initiated by decreased norepinephrine outflow and modulated by variations in end-organ responsiveness, normal subjects being relatively insensitive and patients with essential hypertension being more sensitive as the severity of their hypertension increases.     

Prognostic Value of Computed Tomography Versus Echocardiography Derived Right to Left Ventricular Diameter Ratio in Acute Pulmonary Embolism

BackgroundComputed Tomography (CT) Pulmonary Angiography is the most commonly used diagnostic study for acute pulmonary embolism (PE). Echocardiogram (ECHO) is also used for risk stratification in acute PE, however the diagnostic performance of CT versus ECHO for risk stratification remains unclear.MethodsCT and ECHO right ventricle (RV) and left ventricle (LV) diameters were measured in a retrospective cohort of patients with acute PE. RV:LV diameter ratios were calculated and correlation between CT and ECHO RV:LV ratio was assessed. Sensitivity and specificity for the composite adverse events endpoint of mortality, respiratory failure requiring intubation, cardiac arrest, or shock requiring vasopressors within 30 days of admission were assessed for CT or ECHO derived RV:LV ratio alone and in combination with biomarkers (troponin or B-type natriuretic peptide).ResultsA total of 74 subjects met the inclusion criteria and had a mean age of 62±18 years. The proportion of patients with RV:LV >1 was similar when comparing CT (37.8%) versus ECHO (33.8%) (P = 0.61). A statistically significant correlation was found between CT derived and ECHO derived RV:LV diameter ratio (r = 0.832, P < 0.001). The sensitivity and specificity to predict 30-day composite adverse events for CT versus ECHO derived RV:LV diameter ratio >1 together with positive biomarker status was similar with sensitivity and specificity of 87% and 41% versus 87% and 42%, respectively.ConclusionsIn patients with acute PE, CT and ECHO RV:LV diameter ratio correlate well and identify similar proportion of PE patients at risk for early adverse events. These findings may streamline risk stratification of patients with acute PE.     

Sodium-volume factor, cardiovascular reactivity and hypotensive mechanism of diuretic therapy in mild hypertension associated with diabetes mellitus

Diabetes mellitus is often associated with excess body sodium and frequently accompanied by hypertension. Relationships among blood pressure and various regulatory factors were studied before and after six weeks of diuretic therapy with chlorthalidone, 100 mg/day, in 17 diabetic subjects (aged 32 to 75 years) with borderline to moderate hypertension. Following a four-week placebo phase, mean supine blood pressure was 165/93 ± 26/15 (±SD) mm Hg and exchangeable sodium was increased (49 ± 4 versus 45 ± 4 meq/kg lean body mass in 90 normal subjects; p < 0.01). Blood volume, and supine and upright plasma renin, aldosterone, norepinephrine, epinephrine or dopamine levels were comparable to normal values. Measurements in eight diabetic subjects revealed an increased cardiovascular reactivity, as evidenced by decreased (p < 0.001) pressor doses of norepinephrine (68 ± 42 versus 151 ± 52 ng/kg/min) or angiotensin II (3.9 ± 1.2 versus 10.3 ± 5.5 ng/kg/min). Chlorthalidone decreased blood volume by 11 per cent, lowered body sodium (by 9 per cent) and cardiovascular sensitivity to norepinephrine (by 48 per cent) or angiotensin II (by 60 per cent) towards normal and reduced blood pressure by 11 per cent to 145/82 ± 13/12 mm Hg (11 per cent). Plasma renin and aldosterone were markedly increased by chlorthalidone, whereas plasma and urinary catecholamine levels were not significantly altered. These findings suggest that hypertension in patients with diabetes mellitus may partly depend on increased body sodium and/or an exaggerated cardiovascular reactivity to norepinephrine and angiotensin II. The blood pressure-lowering effect of diuretic therapy may be due to removal of excess sodium and the restoration of norepinephrine pressor sensitivity towards normal without an equivalent increase in adrenergic nervous activity.     

Treatment and Outcomes of Acute Pulmonary Embolism and Deep Venous Thrombosis: The CVRN VTE Study

BackgroundFew studies describe both inpatient and outpatient treatment and outcomes of patients with acute venous thromboembolism in the United States.MethodsA multi-institutional cohort of patients diagnosed with confirmed pulmonary embolism or deep venous thrombosis during the years 2004 through 2010 was established from 4 large, US-based integrated health care delivery systems. Computerized databases were accessed and medical records reviewed to collect information on patient demographics, clinical risk factors, initial antithrombotic treatment, and vital status. Multivariable Cox regression models were used to estimate the risk of death at 90 days.ResultsThe cohort comprised 5497 adults with acute venous thromboembolism. Pulmonary embolism was predominantly managed in the hospital setting (95.0%), while 54.5% of patients with lower extremity thrombosis were treated as outpatients. Anticoagulant treatment differed according to thromboembolism type: 2688 patients (92.8%) with pulmonary embolism and 1625 patients (86.9%) with lower extremity thrombosis were discharged on anticoagulants, compared with 286 patients (80.1%) with upper extremity thrombosis and 69 (54.8%) patients with other thrombosis. While 4.5% of patients died during the index episode, 15.4% died within 90 days. Pulmonary embolism was associated with a higher 90-day death risk than lower extremity thrombosis (adjusted hazard ratio 1.23; 95% confidence interval, 1.04-1.47), as was not being discharged on anticoagulants (adjusted hazard ratio 5.56; 95% confidence interval, 4.76-6.67).ConclusionsIn this multicenter, community-based study of patients with acute venous thromboembolism, anticoagulant treatment and outcomes varied by thromboembolism type. Although case fatality during the acute episode was relatively low, 15.4% of people with thromboembolism died within 90 days of the index diagnosis.     

Pulmonary infarction in sickle cell trait.

A young black man presented with unexplained pleuritic chest pain. A hematologic evaluation revealed sickle cell trait, Chest roentgenograms, ventilation/perfusion lung scanning and a pleural-parenchymal lung biopsy documented pulmonary infarction. Sickle cell trait with resultant pulmonary infarction should be considered in black subjects with unexplained pulmonary diseases.     

TUSARC: Prognostic Value of High-Sensitivity Cardiac Troponin T Assay in Asymptomatic Patients with High Cardiovascular Risk

BackgroundPrognostic value of high-sensitivity cardiac troponin T (hs-cTnT) assays have been assessed in selected populations in different studies and in registries of members of the general population with low cardiovascular risk. The aim of this study was to determine the prognostic value of hs-cTnT in an asymptomatic very-high cardiovascular risk Spanish population.MethodsFrom a previous prospective cohort of the TUSARC (troponina T UltraSensible en pacientes Asintomáticos de alto Riesgo Cardiovascular) registry, follow-up was conducted in 602 patients (93.18%). The association of high hs-cTnT (≥99th percentile value) and incidence of primary event was studied. A primary event was defined as a combined major cardiovascular event (incidence of cardiovascular death, decompensated heart failure, non-fatal cerebrovascular event, non-fatal myocardial infarction, or coronary revascularization). The association between high hs-cTnT and incidence of secondary events was studied as well.ResultsIn patients with high hs-cTnT, the incidence of primary event during follow-up was significantly higher (18.30% vs 3.67% P < .001): heart failure (6.25% vs 0.73% P < .001), cardiovascular death (7.29% vs 0.00% P < .001), and death from any cause (7.81% vs 0.98% P < .001).ConclusionsIn an asymptomatic very-high cardiovascular risk Spanish population, elevated hs-cTnT was significantly associated with incident major cardiovascular combined end point and incidence of heart failure, cardiovascular death, and death from any cause.     

Premature death and associated risk factors in urban middle-aged men

The full range of premature mortality and associated risk factors was analyzed for a follow-up period of three and a half to eight years in a uniform group of 7,935 middle-aged males (46 to 48 years old at screening) participating between the years 1975 and 1979 in the preventive population program in Malmö (participation rate 76.7 percent). Of the 218 deaths that occurred, necropsy was performed in 181 (83.0 percent). Three major causes of death were established: cancer (61/218), alcohol-related deaths (55/218), and coronary heart disease (50/218). In these three main categories of male premature mortality, significant and distinctly differential risk factor patterns were found. In coronary heart disease, smoking (p = 0.0062), serum cholesterol level (p = 0.00014), serum triglyceride level (p = 0.00013), systolic blood pressure (p = 0.000012), and diastolic blood pressure (p = 0.0021) were the strongest single determinants, but the independent role of the diastolic blood pressure disappeared in a multivariate analysis whereas all the others could be combined in a highly predictive logistic model. In the alcohol-related group, equal or stronger risk factor associations were present for serum gamma-glutamyltransferase level (p < 0.0001), questionnaire alcoholism screening response (p < 0.0001) and, inversely, serum cholesterol level (p = 0.0046) and serum creatinine level (p < 0.0001), all of which were independent and could be combined in an even more predictive logistic model than in the coronary heart disease group. In the cancer deaths, significant associations were found for serum urate level (p = 0.023) and, inversely, serum cholesterol level (p = 0.056 ? 0.031). Malignant and alcohol-related diseases constituted at least equally prominent groups as the cardiovascular disorders of the total premature deaths that occurred during middle age in these cohorts of Malmö males. All of these conditions are potentially avoidable and seem to be associated with significant and distinctive risk factor patterns. It seems possible that these factors may be applied, in current alcohol-related disorders and in future malignant diseases, both as indicators of the respective risks and as signals and instruments for directed preventive measures like the previously well established and tested methods for the regulation of blood pressure, serum lipids levels, and so on.     

Acute upper gastrointestinal hemorrhage in patients with chronic renal disease

In order to reassess the role of duodenal ulcers as a cause of acute upper gastrointestinal hemorrhage in patients with chronic renal failure, 20 consecutive patients with moderate to severe chronic renal failure and a comparison group of patients without renal disease who were seen for acute upper gastrointestinal hemorrhage were reviewed. Gastric bleeding sites (gastric ulcer in 35 percent and gastritis in 20 percent) rather than duodenal ulcers were the most common sources of bleeding and were significantly associated with the use of ulcerogenic drugs. Patients with renal disease in whom acute upper gastrointestinal hemorrhage developed had significantly more morbidity and a trend toward higher mortality than the comparison group of patients without renal disease. It is concluded that gastric mucosal lesions, at least in part due to the use of ulcerogenic drugs, are the most common cause of significant acute upper gastrointestinal hemorrhage in patients with chronic renal failure.     

Eosinopenia as an Adverse Marker of Clinical Outcomes in Patients Presenting with Acute Myocardial Infarction

BackgroundEosinopenia is considered a surrogate of inflammation in several disease settings. Following ST-segment elevation myocardial infarction, eosinopenia is presumed to be a marker of infarct severity. We sought to study the relationship between eosinopenia and infarct severity and how this relationship determined the long-term outcomes following ST-segment elevation myocardial infarction.MethodsSix hundred and six consecutive patients undergoing primary percutaneous coronary interventions from a large volume single center were enrolled. Low eosinophil count was defined as < 40 cells/mL from samples within 2 hours after reperfusion. Primary endpoint was defined as composite of death, myocardial infarction, stroke, unplanned revascularization, and readmission for heart failure over 3.5 years’ follow-up.ResultsSixty-five percent of the patients had eosinopenia. Patients in the low eosinophil group had larger infarct size as measured by troponin value (2934 vs 1177 ng/L, P < .001) and left ventricle systolic function on echocardiography (48% vs 50%, P = 0.029). There was a weak correlation between eosinophil count and both troponin (r = -0.25, P < 0.001) and ejection fraction (r = 0.10, P = .017). The primary endpoint was higher in eosinopenic patients (28.8% vs. 20.4%; hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.05 to 2.13, P = .023). A discordance between eosinopenia and severe left ventricle systolic dysfunction was observed in 55.6% of cases. Compared with normal count, eosinopenia was associated with worse clinical outcomes in patients with non-severe left ventricle dysfunction (24.1% vs 16.2%; HR 1.58, 95% CI 1.01 to 2.45, P = .044) but not in those with severe left ventricle dysfunction (42.3% vs. 38.9%; HR 1.10, 95% CI 0.59 to 2.03, P = .77) (P < .01 for interaction).ConclusionsEosinopenia is an easily determined marker that reflects worse clinical outcomes over long-term follow-up.     

Experience with pindolol, a betareceptor blocker, in the treatment of hypertension.

Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, were studied at rest and during work before and after an average of two and 16 months of oral treatment with the beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, both at rest and during work. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: (1) a negative chronotropic effect on the heart, (2) a decrease in peripheral vascular resistance, and (3) an increase in venous capacitance affecting the venous return. However, the significance of these mechanisms seems to differ when the situations after two months of treatment are compared with those after 16 months of treatment. In the beginning, a decrease in cardiac output seems to be the main cause of the lowering of the blood pressure; later, a decrease in systemic vascular resistance might be of greater importance.     

Development of acute erythroleukemia in B-cell immunoproliferative disorders after prolonged therapy with alkylating drugs

The increased incidence of acute myeloblastic leukemia and its variants in patients treated with radiation therapy has long been known. Over the past few years, a relationship between chemotherapy, especially with alkylating agents, and the subsequent development of acute myeloblastic leukemia has been suspected. An unusual variant of acute myeloblastic leukemia, erythroleukemia, has been recognized in three of our patients with B-cell immunoproliferative disorders treated with alkylating agents for extended periods. Review of previously reported cases of myeloblastic transformation after chemotherapy or radiotherapy suggests an inordinately high incidence of the erythroleukemic variant; however, this is not borne out by statistical analysis. The exact relationship between alkylating drug therapy and the development of acute leukemia remains quite speculative.     

Net Clinical Benefit of Non-Vitamin K Antagonist vs Vitamin K Antagonist Anticoagulants in Elderly Patients with Atrial Fibrillation

BackgroundThe risks of thromboembolic and hemorrhagic events in patients with atrial fibrillation both increase with age; therefore, net clinical benefit analyses of anticoagulant treatments in the elderly population are crucial to guide treatment. We evaluated the 1-year clinical outcomes with non-vitamin-K antagonist and vitamin K antagonist oral anticoagulants (NOACs vs VKAs) in elderly (≥75 years) patients with atrial fibrillation in a prospective registry setting.MethodsData on 3825 elderly patients were pooled from the PREFER in AF and PREFER in AF PROLONGATION registries. The primary outcome was the incidence of the net composite endpoint, including major bleeding and ischemic cardiovascular events on NOACs (n = 1556) compared with VKAs (n = 2269).ResultsThe rates of the net composite endpoint were 6.6%/year with NOACs vs 9.1%/year with VKAs (odds ratio [OR] 0.71; 95% confidence interval [CI], 0.51-0.99; P = .042). NOAC therapy was associated with a lower rate of major bleeding compared with VKA use (OR 0.58; 95% CI, 0.38-0.90; P = .013). Ischemic events were nominally reduced too (OR 0.71; 95% CI, 0.51-1.00; P = .050). Major bleeding with NOACs was numerically lower in higher-risk patients with low body mass index (BMI; OR 0.50; 95% CI, 0.22-1.12; P = .07) or with age ≥85 years (OR 0.44; 95% CI, 0.13-1.49; P = .17).ConclusionsOur real-world data indicate that, compared with VKAs, NOAC use is associated with a better net clinical benefit in elderly patients with atrial fibrillation, primarily due to lower rates of major bleeding. Major bleeding with NOACs was numerically lower also in higher-risk patients with low BMI or age ≥85 years.