Oscar Bazzino

Independent Prognostic Value of Elevated C-Reactive Protein in Unstable Angina

BACKGROUND There is growing evidence of the prognostic importance of C-reactive protein (CRP) in unstable angina. However, the independent value of CRP relative to other conventional markers at different stages of treatment has not been established. Therefore, we assessed the in-hospital and 90-day prognostic values of serum CRP in unstable angina. We also compared the relation of CRP at admission and discharge with 90-day outcome. METHODS AND RESULTS One hundred ninety-four consecutive patients were included in a derivation (n = 105) and a validation set (n = 89). Serum CRP was measured at admission, at 48 hours, and at hospital discharge. A cutoff point of 1.5 mg/dL for CRP provided optimum sensitivity and specificity for adverse outcome, based on the receiver operator curves. No association was found between CRP on admission and in-hospital outcome. CRP at admission, adjusted for age, ECG findings on admission, silent ischemia, left ventricular wall motion score, and high-risk clinical presentation, was related to the combined end point of refractory angina, myocardial infarction, or death at 90 days (hazard ratio [HR] 1.9, 95% CI 1.2 to 8.3, P = 0.002). CRP at hospital discharge was the strongest independent marker of an adverse outcome (HR 3.16, 95% CI 2.0 to 5.2, P = 0.0001). These results were confirmed in the validation set (CRP at discharge: HR 3. 3, 95% CI 2.0 to 7.69, P = 0.0001). CONCLUSIONS In unstable angina, CRP is a strong independent marker of increased 90-day risk. Compared with CRP at admission, CRP at discharge is better related to later outcome and could be of great utility for risk stratification.

Prospective Validation of the Prognostic Usefulness of Brain Natriuretic Peptide in Asymptomatic Patients With Chronic Severe Mitral Regurgitation

OBJECTIVES The purpose of the study was to determine the independent and additive prognostic value of brain natriuretic peptide (BNP) in patients with severe asymptomatic mitral regurgitation and normal left ventricular function. BACKGROUND Early surgery could be advisable in selected patients with chronic severe mitral regurgitation, but there are no criteria to identify candidates who could benefit from this strategy. Assessment of BNP has not been studied in asymptomatic patients with severe mitral regurgitation; hence, its prognostic value remains unclear. METHODS We prospectively evaluated 269 consecutive patients with severe asymptomatic organic mitral regurgitation and left ventricular ejection fraction above 60%. The first 167 consecutive patients served as the derivation cohort, and the following 102 patients served as a validation cohort. The combined end point was the occurrence of either symptoms of congestive heart failure, left ventricular dysfunction, or death at follow-up. RESULTS The end point was reached in 35 (21%) patients of the derivation set and in 21 (20.6%) patients of the validation cohort. The receiver-operating characteristics curve yielded an optimal cutoff point of 105 pg/ml of BNP that was able to discriminate patients at higher risk in both cohorts (76% vs. 5.4% and 66% vs. 4.0%, respectively). In both sets, BNP was the strongest independent predictor by multivariate analysis. CONCLUSIONS Among patients with severe asymptomatic organic mitral regurgitation, BNP > or =105 pg/ml discriminates a subgroup of patients at higher risk. Because of its incremental prognostic value, BNP assessment should be considered in clinical routine workup for risk stratification.

A Multicenter, Randomized Study of Argatroban Versus Heparin as Adjunct to Tissue Plasminogen Activator (TPA) in Acute Myocardial Infarction: Myocardial Infarction With Novastan and TPA (MINT) Study

OBJECTIVES This study examined the effect of a small-molecule, direct thrombin inhibitor, argatroban, on reperfusion induced by tissue plasminogen activator (TPA) in patients with acute myocardial infarction (AMI). BACKGROUND Thrombin plays a crucial role in thrombosis and thrombolysis. In vitro and in vivo studies have shown that argatroban has advantages over heparin for the inhibition of clot-bound thrombin and for the enhancement of thrombolysis with TPA. METHODS One hundred and twenty-five patients with AMI within 6 h were randomized to heparin, low-dose argatroban or high-dose argatroban in addition to TPA. The primary end point was the rate of thrombolysis in myocardial infarction (TIMI) grade 3 flow at 90 min. RESULTS TIMI grade 3 flow was achieved in 42.1% of heparin, 56.8% of low-dose argatroban (p = 0.20 vs. heparin) and 58.7% of high-dose argatroban patients (p = 0.13 vs. heparin). In patients presenting after 3 h, TIMI grade 3 flow was significantly more frequent in high-dose argatroban versus heparin patients: 57.1% versus 20.0% (p = 0.03 vs. heparin). Major bleeding was observed in 10.0% of heparin, and in 2.6% and 4.3% of low-dose and high-dose argatroban patients, respectively. The composite of death, recurrent myocardial infarction, cardiogenic shock or congestive heart failure, revascularization and recurrent ischemia at 30 days occurred in 37.5% of heparin, 32.0% of low-dose argatroban and 25.5% of high-dose argatroban patients (p = 0.23). CONCLUSIONS Argatroban, as compared with heparin, appears to enhance reperfusion with TPA in patients with AMI, particularly in those patients with delayed presentation. The incidences of major bleeding and adverse clinical outcome were lower in the patients receiving argatroban.

N-Terminal B-Type Natriuretic Peptide Assessment Provides Incremental Prognostic Information in Patients With Acute Coronary Syndromes and Normal Troponin T Values Upon Admission

OBJECTIVES The purpose of this study was to determine the prognostic value of N-terminal B-type natriuretic peptide (NT-proBNP) in two independent samples of patients presenting with acute coronary syndromes (ACS) and normal troponin T (TnT) values. BACKGROUND Recently assessment of NT-proBNP has been studied in patients with ACS. However, the clinical relevance in patients who present without troponin elevation is unclear. METHODS We included 2,614 patients from two independent registries, one serving as a derivation cohort comprising patients with evident ACS (Bad Nauheim ACS registry, n = 1,131) and the other serving as a validation cohort including chest pain patients (PACS [Prognosis in Acute Coronary Syndromes] registry, n = 1,483). NT-proBNP and TnT were measured upon admission. Clinical outcome has been assessed over a 6-month period. RESULTS In both cohorts, the mortality rate was significantly lower among TnT negative patients: 3.8% versus 8.2% (p = 0.009) in the Bad Nauheim ACS registry, and 2.8% versus 8.6% (p = 0.009) in the PACS registry. Among TnT negative patients, receiver-operating characteristics curve analysis yielded an optimal cutoff value of 474 pg/ml for NT-proBNP that was able to discriminate patients at higher risk in the Bad Nauheim ACS and PACS registries (mortality rate 12.3% vs. 1.3%, p < 0.001 and 8.5% vs. 1.5%, p < 0.001, respectively). By Kaplan-Meier analysis, patients with NT-proBNP values over 474 pg/ml were at higher risk for death in the Bad Nauheim ACS registry (log-rank 19.01, p < 0.001, adjusted hazard ratio [HR] 9.56 [95% confidence interval (CI) 2.42 to 37.7], p = 0.001) and in the PACS registry (log-rank 23.16, p < 0.001, adjusted HR 5.02 [95% CI 2.04 to 12.33], p < 0.001). CONCLUSIONS Among patients with suspected ACS considered to be at low risk because of normal troponin values, NT-proBNP above 474 pg/ml is able to discriminate individuals at higher risk. Because of its incremental prognostic value, NT-proBNP assessment should be considered in clinical routine for risk stratification of patients with normal troponin.

Preoperative 6-minute walk test adds prognostic information to Euroscore in patients undergoing aortic valve replacement

Aims: The authors investigated the additive prognostic value of the 6-minute walk test (6MWT) to Euroscore in patients with severe aortic stenosis undergoing aortic valve replacement (AVR) Methods and results: 208 patients with severe AS underwent the 6MWT before AVR, as part of a randomised trial (ASSERT) comparing stented and stentless aortic valves. Clinical follow-up was available for 200 patients up to 12 months. The rate of death, myocardial infarction (MI) or stroke (time to first event) was 13% (n = 14) in patients walking <300 metres compared to 4% (n = 4) in those who walked ⩾300 metres (p = 0.017). When rate of death, MI or stroke by Euroscore risk was stratified by 6-minute walking distance, the 6MWT added prognostic information. In a Cox regression analysis 6MWT distance was the only variable retained as an independent predictor of the composite outcome of death, MI or stroke at 12 months (HR 0.28 95% CI 0.09 to 0.85, p = 0.025). Conclusions: The 6MWT is safe and feasible to carry out in patients with severe aortic stenosis before AVR, and provides potentially important functional and prognostic information to clinical assessment and the Euroscore risk score.

C-reactive protein and the stress tests for the risk stratification of patients recovering from unstable angina pectoris.

We assessed the 90-day prognostic value of stress tests and C-reactive protein (CRP) after medical stabilization of unstable angina. We included 139 consecutive patients with unstable angina who were free of complications or did not undergo revascularization during hospitalization. Blinded CRP assays and a stress test (95 exercise electrocardiograms, 44 dobutamine echocardiograms) were performed within the first week after discharge. Of 139 participants, 44 (31.6%) had an ischemic stress test response. CRP was elevated (> 1.5 mg/dl) in 40 patients (28.7%). CRP >1.5 mg/dl was more frequently observed among patients who experienced death or myocardial infarction at 90 days (88.2% vs 20.5%, p <0.0001). Compared with the stress tests, CRP showed greater sensitivity (88% vs 47%) and specificity (81% vs 70%) for increased risk, and higher positive (37.5% vs 18.2%) and negative (98% vs 90%) predictive values. The area under the receiver operating curve of the relation with the 90-day outcome increased from 0.58 +/- 0.07 to 0.83 +/- 0.05 when the CRP data were added to the stress tests results (p <0.001). Elevation of CRP differentiated stress tests negative patients with increased risk of major events during follow-up. In patients who respond to medical treatment for unstable angina, CRP elevation may be a better parameter than the stress test in identifying the presence of persistent plaque instability.

Valor pronóstico de la determinación de la proteína C reactiva en la angina inestable

El mecanismo desencadenante de la angina inestablees la interrupcion transitoria de la perfusion miocardicapor un trombo superpuesto a una placa ateroscleroticacoronaria fisurada. Recientemente se ha identificado unproceso inflamatorio que precede a la rotura endotelial yque puede desempenar un papel desencadenante y/operpetuador de los fenomenos descritos, alterando la adhesividaddel endotelio para los leucocitos o plaquetas, yestimulando la actividad procoagulante y vasoconstrictoradel endotelio. La existencia de este mecanismo inflamatorio se sustentaen evidencias histologicas, hematologicas, y humorales,entre ellas, la existencia de niveles altos de proteinaC reactiva (PCR), una de las proteinas plasmaticascuya concentracion aumenta mas del 25% durante el fenomenoinflamatorio. Varios estudios de angina inestable han demostrado elaumento de la concentracion serica de marcadores de inflamacioncomo PCR y amiloide A, asi como una asociacionentre el nivel de PCR basal y el pronostico ulterior.Como resumen puede mencionarse que el aumento delvalor de PCR es un predictor independiente de evolucionadversa en pacientes con angina inestable o infarto sinonda Q. Ademas, la persistencia del aumento del nivel dePCR podria tener mayor valor pronostico que el aumentotransitorio. Se ha observado valor pronostico aditivo entrePCR y troponinas. Aunque la valoracion clinica es fundamental para la estimaciondel riesgo, los marcadores sericos como la PCRpueden ser utiles para complementar la informacion delas pruebas convencionales.

Early treatment with low-dose enalapril after acute myocardial infarction: An Equilibrium radionuclide angiographic study☆

BackgroundTo further elucidate the mechanisms involved in the treatment of acute myocardial infarction (AMI) with angiotensin-converting enzyme inhibitors, we compared the effects on left ventricular volumes of early (<48 hours) versus late (45 days) administration of a fixed low dose of enalapril (10 mg) in patients with AMI. We also analyzed the changes of left ventricular volumes after withdrawal of the study drug. Reduced dilation of the left ventricle is one of the beneficial effects of angiotensin-converting enzyme inhibition after AMI. However, the nature of this effect is not completely understood.Methods and ResultsWe included 89 patients within 48 hours after onset of a first AMI and radionuclide left ventricular ejection fraction less than 45%. The study was double-blind and compared enalapril and placebo with a crossover design. All patients were randomly assigned to a sequence A (enalapril, 45 days; placebo, 45 days) or B (placebo, 45 days; enalapril, 45 days). The end point was the change of left ventricular volume at 45 and 90 days. Thrombolysis was administered to 26 patients (70%) in group A and 25 (75%) in group B. All pretreatment clinical variables were similar in both groups. Median and 95% confidence intervals (CIs) of left ventricular diastolic volumes were 46.8 ml/m2 (39 to 61 ml/m2) and 46.6 ml/m2 (39 to 60 ml/m2) for groups A and B, respectively. Baseline end systolic volumes were 28.5 ml/m2 (20 to 36 ml/m2) and 28.9 ml/m2 (23 to 28 ml/m2) in the same groups. Placebo treatment during the initial 45 days was associated with an increase of left ventricular diastolic volume of 8.75 ml/m2 (95% CI, 3.25 to 17.1 ml/m2; p<0.01) and end-systolic volume of 4.20 ml/m2 (95% CI, 0.00 to 10.1 ml/m2; p<0.05). No significant changes during other phases of the study were observed. At 45 days left ventricular diastolic volume was 11.1 ml/m2 (95% CI, 0.5 to 2.2 ml/m2), greater in placebotreated patients compared with patients receiving enalapril.ConclusionsIn patients with a first Q wave AMI and left ventricular ejection fraction less than 45%, treatment with enalapril can prevent left ventricular dilation. This protective effect involves at least partially a structural modification of the left ventricle. Hence, maximal benefit can be obtained only with early initiation of treatment.