Risk of placenta-mediated pregnancy complications or pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and heterozygosity for factor V Leiden or G20210 prothrombin mutation.

BACKGROUND: Few studies have evaluated the risk of pregnancy-related adverse events in asymptomatic relatives of probands for VTE and factor V Leiden or the G20210A variant. The antepartum management of this population ranges from antepartum anticoagulation therapy to clinical surveillance. OBJECTIVE: To evaluate the risk of placenta-mediated pregnancy complications and pregnancy-related VTE in VTE-asymptomatic families of probands with VTE and who are heterozygous carriers of either factor V Leiden or PT-G20210A mutation. METHODS: One hundred and fifty-eight relatives, who had 415 pregnancies, were retrospectively evaluated. Odds ratios and 95% confidence intervals were calculated to compare pregnancy outcomes between women with and without thrombophilia. RESULTS: In the factor V Leiden group, 22 placenta-mediated pregnancy events of 152 pregnancies (14.4%) were reported, compared with 25 adverse events of 172 pregnancies in the G20210A prothrombin group (14.5%) and 13 adverse events of 91 pregnancies in the non-carrier group (14.2%). Carriers of factor V Leiden or G20210A prothrombin were not associated with a higher risk of pregnancy-adverse outcomes compared with non-carriers: OR 1.02 (95% CI, 0.40-2.25) and 1.25 (95% CI, 0.48-3.24), respectively. Four episodes of pregnancy-associated VTE of 415 pregnancies (0.96%) were recorded. Two episodes of VTE in the G20210A group, one in the factor V Leiden group, and one episode in the non-carrier group were noted. CONCLUSIONS: In VTE-asymptomatic relatives of probands with VTE, the presence of factor V Leiden or the G20210A prothrombin mutation in heterozygosis should not lead to a decision to instigate antepartum prophylaxis.

Characteristics and outcome of acute myocardial infarction in young patients. The PRIAMHO II study.

BACKGROUND: The objective was to analyze the incidence, risk factors, management, and complications of acute myocardial infarction (AMI) in the young patient in Spain. METHODS: Clinical characteristics, treatment, and outcome were analyzed in patients younger than 45 years admitted with an AMI diagnosis to the Coronary Units of 58 Spanish hospitals from 15th May to 15th December 2000. RESULTS: Six thousand two hundred and ten consecutive patients were registered, 7% out of them were <45 years old. Outcome was better in the younger group, with a lower mortality rate at 28 days (3.7 vs. 11.9%; p < 0.001), demonstrating that age <45 years is an independent protective factor for mortality (relative risk: 0.41; 95% CI: 0.23-0.73; p < 0.001). This difference remained at 1-year follow-up. CONCLUSIONS: AMI in young patients presents distinct clinical characteristics, a different treatment, management and outcome with respect to the older group.

Short- and long-term prognostic value of the corrected QT interval in the non-ST-elevation acute coronary syndrome.

BACKGROUND AND PURPOSE: Myocardial ischemia prolongs the QTc interval. Very little data exists about its prognostic implications in the non-ST-elevation acute coronary syndromes (NST-ACS). METHODS: This is and observational and prospective study in which we evaluated the prognostic implications of the QTc obtained at admission (AQTc) in the short- and long-term of the NST-ACS. The median of the follow-up was 17 months. RESULTS: AQTc correlated adequately with the incidence of adverse events in the short- and long-term (P < .001), with the best cut-off point in 450 milliseconds. Patients with AQTc > or =450 presented higher frequency of in-hospital death: 8.8% vs 1.2%; P = .001, and MACE (death, recurrent ischemia, or urgent coronary revascularization): 72% vs 25%; P < .001. In a Cox regression analysis, we found 3 independent predictors of cardiovascular death after discharge: AQTc > or =450 (14.7% vs 2.1%; P < .0001), age >65 years and left ventricular ejection fraction <40%. Coronary revascularization reduced the risk of posthospitalary cardiovascular death in AQTc > or =450 milliseconds (5% vs 24%; P < .0001) but had no significant effect in AQTc<450 milliseconds. CONCLUSION: These findings provide a new evidence supporting the prognostic value of the AQTc in predicting unfavorable events in the short- and long-term of the NST-ACS.

Hemorrhagic pericardial effusion as the debut of acquired hemophilia in a chronic lymphocytic leukemia patient: A case report, and a review of acquired hemophilia A-related hematological malignancies.

BACKGROUND: Acquired hemophilia A (AHA) is a rare bleeding disease caused by autoantibodies against factor VIII. Spontaneous bleeding symptoms usually affect the skin and muscle, while pericardial effusion is an extremely rare manifestation. In the elderly, anticoagulant treatment is frequent and bleeding symptoms are usually associated with this. CLINICAL FINDINGS: We report a hemorrhagic pericardial effusion as the AHA debut in a patient with untreated chronic lymphocytic leukemia and anticoagulated with apixaban for atrial fibrillation and chronic arterial ischemia. The patient was treated with recombinant activated factor VII to control the active bleeding and corticosteroids and cyclophosphamide to eradicate the inhibitor. In addition, a briefly review of hematological malignancies associated to acquired hemophilia was performed. PARTICULARITIES:: a) anticoagulant treatment may confuse the suspicion of AHA and its diagnosis; b) hemorrhagic pericardial effusion is an extremely rare presentation; c) bypassing agents raise the risk of thromboembolism; d) hematological malignancies rarely cause AHA (<20% of cases). CONCLUSION: A multidisciplinary team is needed to diagnose and manage AHA effectively. The use of anticoagulants may lead to the misdiagnosis of clinical symptoms. Chronic lymphocytic leukemia is one of the main causes of hematological malignancies associated. The specific treatment of CLL is still recommended in the event of active disease.

[Kinetics of C-reactive protein release in different forms of acute coronary syndrome]. / Cinética de la proteína C reactiva en las distintas manifestaciones clínicas del síndrome coronario agudo.

INTRODUCTION AND OBJECTIVES: Better knowledge of C-reactive protein (CRP) kinetics could lead to improved clinical application of this biomarker. METHODS: We studied 110 patients: 42 had ST-elevation acute myocardial infarction (STEMI), 35 had non-ST-elevation acute myocardial infarction (NSTEMI), and 33 had unstable angina. Patients were admitted to our institution within 6 hours of symptom onset. The levels of CRP, troponin-I, and creatine kinase MB fraction (CK-MB) were measured on admission and every 6 hours during the first 48 h. The CRP level was also measured daily until hospital discharge. RESULTS: The median (interquartile range) CRP level increased relative to baseline from 6 hours after admission, from 5 (2-9) mg/L to 6 (3-10) mg/L (P=.004). Although, CRP levels on admission were similar in all groups, there was a significant difference in peak CRP level: it was 67 (36-112) mg/L in the STEMI group, 29 (20-87) mg/L in the NSTEMI group, and 18 (12-36) mg/L in the unstable angina group. The maximum CRP level was observed 49 (38-53) hours after the onset of symptoms, but occurred later in patients with STEMI. Although there was only a weak non-significant correlation between CRP and troponin levels (r=0.135) at admission, the maximum CRP level was found to be influenced by the degree of myocardial damage (r=0.496; P< .001). CONCLUSIONS: The pattern of CRP release observed was clearly different in different forms of acute coronary syndrome. Although the CRP level measured at admission was similar in all patient groups, it was influenced by the degree of early myocardial tissue necrosis. This variation in CRP kinetics should be taken into consideration when designing future studies.

[Reduction in acute myocardial infarction mortality over a five-year period]. / Reducción de la mortalidad por infarto agudo de miocardio en un período de 5 años.

INTRODUCTION AND OBJECTIVES: To assess recent changes in the management of patients with acute myocardial infarction (AMI) and their impact on mortality using data from the PRIAMHO I and II registries (1995 and 2000). PATIENTS AND METHOD: Of the 168 public hospitals in Spain, 24 and 58 contributed to the 1995 and 2000 PRIAMHO registries, respectively. RESULTS: Patients in the PRIAMHO II registry (n=6221) were significantly older, more often female, and proportionally more likely to have coronary risk factors or a previous myocardial infarction, or to have undergone revascularization than those in PRIAMHO I (n=5242). Reperfusion therapy was administered more often (46.9% vs 41.9%, P<.001) and earlier (48 min vs 60 min, P<.001). Antiplatelet drugs were given to 96.1% vs 89.1% of patients, beta-blockers to 51.1% vs 30.1%, and ACE inhibitors to 41.6% vs 24.9% (P<.001 for all comparisons). In addition, 28-day mortality was 11.3% and 14.2% (P<.001), respectively, and one-year mortality, 16.4% and 18.5% (P<.001), respectively. The adjusted hazard ratio for mortality at one year in PRIAMHO II compared with PRIAMHO I was 0.78 (95% CI, 0.70-0.86, P<.001; adjusted for age, sex, diabetes, smoking, dyslipemia, hypertension, previous MI and CABG, ST-elevation status and Killip class at admission, and hospital characteristics). CONCLUSIONS: Even though patients registered in 2000 formed a higher risk group than those registered in 1995, one-year mortality after AMI decreased by 22% over the five-year period. This improvement was due to more frequent and earlier reperfusion therapy and better use of antithrombotics, beta-blockers and ACE inhibitors.

[Management of myocardial infarction in Spain in the year 2000. The PRIAMHO II study]. / Tratamiento del infarto agudo miocardio en España en el año 2000. El estudio PRIAMHO II.

INTRODUCTION AND OBJECTIVES: Hospital registries are useful tools to measure the degree of implementation of new treatments and clinical practice guidelines. PATIENTS AND METHOD: The hospital registry described here was developed in the prospective PRIAMHO II study, which involved a random selection of Spanish hospitals with a coronary intensive care unit and external quality control. This study investigated patients admitted to the coronary care unit with acute myocardial infarction. Demographic and clinical characteristics were recorded, as well as the management, clinical course and survival after 28 days and one year. RESULTS: From May 15 to December 15 2000 we included in the registry 6,221 patients from the 58 hospitals that complied with the quality control requirements (71.6% of all participating hospitals). Acute mortality was 9.6%; 28-day and one-year mortality were 11.4% and 16.5%, respectively. Of the patients with ST elevation-myocardial infarction of less than 12 hours' duration, 71.6% were reperfused and 89.3% received fibrinolysis with a median door-to-needle time of 48 minutes. Ejection fraction was measured in 81% of the patients, and 43% were tested for inducible ischemia. About nine-tenths (91%) of the patients were discharged on least one antiplatelet drug, 56% on a beta blocker, 45% on an ACE inhibitor, and 45% on a lipid-lowering agent, with a coefficient of variation between hospitals greater than 25% for the last three drugs. CONCLUSIONS: The percentage of patients with ST elevation treated with reperfusion should increase, as it probably will thanks to the increasing use of primary angioplasty. The door-to-needle time was longer than the recommended interval. In-hospital risk stratification was good but nonsystematic for the evaluation of ejection fraction, and unsatisfactory for inducible ischemia testing. At discharge the percentages of patients receiving beta blockers, ACE inhibitors and statins were not optimal, and there were wide variations in prescribing practices between hospitals.

[Long-term prognostic value of troponin I in patients admitted to a coronary unit for unstable angina]. / Valor pronóstico de la troponina I en los pacientes ingresados en una unidad coronaria por angina inestable.

INTRODUCTION AND OBJECTIVES: Troponin I (TnI) is a useful marker of myocardial damage for the diagnosis and prognosis of acute coronary syndrome. The purpose of this study was to analyze the long-term prognostic value of the peak TnI concentration obtained within 48 h of admission to the coronary unit for unstable angina. METHODS: The study included 149 consecutive patients. Serial determinations were made of the MB fraction of creatine kinase (CK-MB) and TnI. Patients without CK-MB elevation were classified into two groups depending on the presence of high (n = 58) or normal (n = 91) troponin I values. We prospectively analyzed the clinical and evolutive factors related to the probability of death, new acute coronary event, or coronary revascularization at one-year of follow-up. RESULTS: There were no differences in the clinical characteristics between groups, except that patients in the group with high TnI values were older (69 vs. 64 years, p = 0.01). At one year of follow-up there were no differences in the incidence of new acute coronary events or coronary revascularization procedures; however there was a higher mortality in the group with high TnI (13 vs. 4%; p = 0.01). The independent predictors of mortality were prior myocardial infarction (RR = 3), elevated troponin I (RR = 3.2), left ventricular ejection fraction < 35% (RR = 10), and age > 70 years (RR = 15). CONCLUSIONS: In patients with unstable angina a high troponin I value in the first 48 h of admission was associated with a higher mortality rate at one-year of follow-up.

In-hospital prognosis in non-ST-segment elevation acute coronary syndrome derived using a new risk score based on electrocardiographic parameters obtained at admission.

Several electrocardiographic variables are of prognostic value in non-ST-segment elevation acute coronary syndrome (NSTEACS). From observations in 427 patients, we developed a new risk score (the ECG-RS) based on admission ECG findings that can be used to determine the likelihood of death or recurrent ischemia during hospitalization, which occurred in 36% of patients. Logistic regression analysis, which considered seven electrocardiographic variables and variables from the Thrombolysis in Myocardial Infarction (TIMI) risk score, identified the following significant predictors: corrected QT interval (QTc) > or =450 ms (odds ratio 4.2, P< .001), ST-segment depression >0.5 mm (odds ratio 2.7, P< .001), and left atrial enlargement (odds ratio 1.8, P =.005). After taking the odds ratios into consideration, we awarded 3 points for a QTc > or =450 ms, 2 points for ST-segment depression >0.5 mm, and 1 point for left atrial enlargement. When patients were divided into three groups on the basis of their ECG-RSs (i.e. < or =1, 2-3 and > or =4), the risk of death or recurrent ischemia was significantly different between the groups, at 11%, 27% and 58%, respectively (P< .001). In conclusion, the new ECG-RS provides a simple, rapid and accurate means of determining prognosis in patients with NSTEACS.

Relationship between the QTc interval at hospital admission and the severity of the underlying ischaemia in low and intermediate risk people studied for acute chest pain.

BACKGROUND: The corrected QT interval (QTc) is prolonged in the setting of acute coronary artery disease. However, very little data are available concerning the relationship between the QTc obtained soon after an episode of acute chest pain (ACHP) and the magnitude and severity of the myocardial ischaemia objectified in subsequent stress tests (STS). METHODS: This was a prospective and observational study in which we investigated the relationship between the QTc determined on the hospital admission electrocardiogram (AQTc) using Bazett's formula and the results of the STS performed subsequently in 206 patients consecutively admitted to the Emergency Department for ACHP without persistent ST-elevation. RESULTS: The mean AQTc was 456+/-60 ms. There were 88 (42%) individuals with a moderately or severely abnormal STS. The AQTc was longer in the patients with a moderately or severely abnormal STS: 490+/-52 versus 430+/-56 (p<0.001) and was correlated with the probability of the patient having a moderately or severely abnormal STS (c=0.84; p<0.001). The best cut-off point was 450 ms (sensitivity, specificity and negative predictive value: 81, 77 and 84 %). Patients with AQTc>or=450 had a higher frequency of moderately or severely abnormal STS (73 versus 16%; OR: 2.9; 95% CI: 2.1-4.1; p<0.001). After adjusting for age, sex, cardiac risk factors, cardiac history, QRS duration, ST-depression, troponin I release and pre-STS medical treatment, AQTc>or=450 remained as an independent predictor (OR: 12; 95% CI: 6-24; p<0.001). CONCLUSIONS: In patients studied for ACHP, the QTc on the hospital admission electrocardiogram correlates with the underlying myocardial ischaemia. AQTc>or=450 ms selects a group of people at risk of presenting a moderately or severely abnormal STS, regardless of ST abnormalities and troponin release.

Relationship between QRS duration and prognosis in non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Previous studies have shown that prolonged QRS duration increases the risk of death in patients with heart failure and after an ST-segment elevation acute myocardial infarction. Very little data exist about the prognostic implications of QRS duration in the non-ST-segment elevation acute coronary syndrome (NST-ACS): unstable angina and non-ST elevation acute myocardial infarction (non-STEMI). METHODS: This is a prospective and observational study in which we included 502 patients (age 71+/-10 years, 68% males, 29% diabetes) consecutively admitted for NST-ACS. QRS duration was manually measured from the 12-lead electrocardiogram. Our aim is to assess the relation between the QRS duration on admission (QRSd) and the risk of cardiovascular death (CvD) in the long-term. RESULTS: Mean QRSd was: 93+/-19 ms. After a median follow-up of 450 days, the cumulative incidence of CvD was: 17.8%. QRSd correlated with the incidence of CvD during the follow-up period: c=0.72 (p<0.001). The best cut-off point was 90 ms (sensitivity, specificity and negative predictive value of QRSd>or=90 ms for CvD: 82, 68 and 93%). According to the Kaplan-Meier analysis, QRSd>or=90 ms was associated with an increase in the risk of CvD: 26.6% versus 7.2% (log rank: 28.6; p<0.001). Cumulative incidence of CvD was higher in QRSd>or=90 ms in patients with unstable angina: 15.5% versus 4% (p=0.02), and in those with non-STEMI: 30.5% versus 8.9% (p<0.001). After adjusting for other significant variables (Cox-regression analysis), QRSd>or=90 ms persisted as an independent predictor for overall CvD (Hazard Ratio: 2.62; 95% Confidence Interval: 1.44-4.74; p<0.001). CONCLUSION: In NST-ACS, the QRSd, even in the normal range, has prognostic implications. QRSd>or=90 ms is independently associated with an increased risk of CvD in the long-term.

Identification of serum endoglin as a novel prognostic marker after acute myocardial infarction.

Endoglin is a proliferation-associated and hypoxia-inducible protein expressed in endothelial cells. The levels of soluble circulating endoglin and their prognostic significance in patients with acute myocardial infarction (AMI) are not known. In this observational prospective study serum endoglin levels were measured by ELISA in 183 AMI patients upon admission to hospital and 48 hrs later and in 72 healthy controls. Endoglin levels in AMI patients on admission were significantly lower than in healthy controls (4.25 +/- 0.99 ng/ml versus 4.59 +/- 0.87 ng/ml; P= 0.013), and decreased further in the first 48 hours (3.65 +/- 0.76 ng/ml, P < 0.001). Upon follow-up (median 319 days), patients who died had a significantly greater decrease in serum endoglin level over the first 48 hrs than those who survived (1.03 +/- 0.91 versus 0.54 +/- 0.55 ng/ml; P= 0.025). Endoglin decrease was an independent predictor of short-term (30 days) (hazard ratio 2.33;95% CI = 1.27-4.23; P= 0.006) cardiovascular mortality, and also predicts overall cardiovascular mortality during the follow-up (median 319 days) in AMI patients (hazard ratio 2.13;95% CI = 1.20-3.78; P= 0.01). In conclusion, early changes in serum endoglin may predict mortality after AMI.

Homocysteine and outcome in young patients with acute coronary syndromes.

BACKGROUND: Despite the well-known pro-thrombotic and pro-inflammatory plasma homocysteine effects, it remains uncertain whether these effects can be associated with an adverse cardiac outcome in young patients admitted with acute coronary syndromes. METHODS: Homocysteine levels were determined within 24 h after admission in 244 consecutive patients aged less than 56 years who presented with an acute coronary syndrome. We evaluated the relationship between homocysteine and both short-term (death, myocardial [re]infarction), and long-term prognosis (death, recurrent acute coronary syndrome and/or ischemic stroke), after 3.4+/-1.7 years of follow-up. RESULTS: Homocysteine levels were similar in patients both with and without in-hospital event: 8.65 (5.36-10.48) vs. 8.98 (7.38-11.13) micromol/l, p=NS. However, patients who presented with the combined event during follow-up had higher homocysteine levels than those free of the event: 10.54 (7.90-11.76) micromol/l vs. 8.52 (7.11-10.23) micromol/l, p=0.001. Patients who either died (13.78 vs. 8.87 micromol/l, p=0.012) or had a myocardial infarction (10.75 vs. 8.76 micromol/l, p=0.006) or unstable angina (10.46 vs. 8.76, p=0.006) during follow-up had higher homocysteine levels. According to the Cox regression analysis: age [hazard ratio 1.05, CI 95%, 0.99-1.10], left ventricular ejection fraction < or =40% [hazard ratio 1.93, CI 95%, 0.98-3.79], and homocysteine tertile 3 [hazard ratio 2.05, CI 95%, 1.13-3.71] were the significant determinants of the combined adverse event during follow-up. Although 41 (18%) of patients presented the TT genotype of the methylen-tetrahydrofolate-reductase thermolabile variant mutation, its occurrence had a neutral effect on morbid-mortality. CONCLUSIONS: High homocysteine levels at admission strongly predict late cardiac events in young patients with acute coronary syndromes.

Relationship between C-reactive protein and the electrocardiographic pattern on admission in patients with acute coronary syndrome.

BACKGROUND: In patients with acute coronary syndrome (ACS), the prevalence of a primary inflammatory pathogenic component of coronary instability, as detectable by elevated C-reactive protein (CRP), varies considerably. The aim of the present study was to assess the prevalence of inflammation in patients with ACS according to the different electrocardiographic (ECG) patterns on admission. METHODS: Hundred and thirty-six consecutive patients with the diagnosis of acute myocardial infarction were divided in three groups according to the ECG pattern on admission. Group 1 included 59 patients with ST segment elevation, group 2 included 50 patients with ST depression and/or T wave inversion and group 3 included 27 patients with no ECG changes. CRP was measured on admission in all patients. For the prevalence of inflammation analysis, we used a cutoff value of 3 mg/l. RESULTS: CRP was above cutpoint significantly more often in patients with ST depression and/or T wave inversion (44.1% in group 1, 70% in group 2 and 40.7% in group 3; p=0.009). Patients with similar ECG pattern and CRP levels above the cutpoint presented a poorer outcome (coronary death, myocardial infarction and recurrence of instability) at one-year follow-up: 54 versus 27% for group 1, 74 versus 27% for group 2 and 45 versus 31% for group 3. CONCLUSIONS: Patients with ST depression and/or T wave inversion on admission exhibit a higher prevalence of elevated CRP than those with ST elevation or no ECG changes, suggesting an important heterogeneity of the role of inflammatory triggers of the clinical syndromes of coronary instability.