Geographic differences in outcomes in outpatients with established atherothrombotic disease: results from the REACH Registry.

AIMS: There are major differences in the prevalence and management of patients with atherothrombotic disease including coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) across different geographical regions. There is, however, little data allowing comparisons of management and outcomes across broad geographic regions. We aimed to describe geographical differences in baseline characteristics, management and outcomes in stable outpatients with established atherothrombotic disease. METHODS AND RESULTS: From the REACH Registry of atherothrombosis, patients with documented CAD, PAD or CVD and with 4-year follow-up were included. Baseline characteristics, treatments and 4-year outcomes were recorded. Event rates were compared between geographical regions and were adjusted for risk scores predicting ischemic and bleeding events. The analyses of baseline characteristics and medications according to geographical region showed marked differences. For the composite primary outcome (cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke), rates ranged from 12.1% in Japan to 18.2% in Eastern Europe. After adjustment, substantial variations remained: taking North America as a reference, patients from Western Europe and Japan had a lower risk of primary outcome event (hazard ratio (HR) 0.93; p = 0.045, and HR = 0.67; p < 0.001 respectively) whereas patients from Eastern Europe had a higher risk (HR = 1.24; p < 0.001). There were no obvious differences between patients from North America and those from Latin America, the Middle East and Asia. CONCLUSION: There are important variations in the outcomes of patients with atherothrombotic across geographic regions. These observations have important implications for public health and clinical research.

Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

Valor pronóstico de la hiperuricemia en la insuficiencia cardiaca crónica / Prognostic value of hyperuricemia in chronic heart failure

BACKGROUND: Hyperuricemia has been proposed as a risk marker in chronic heart failure, but its value as an independent prognostic is not well established. AIM: To determine the prognostic value of hyperuricemia, in patients with chronic stable heart failure. PATIENTS AND METHODS: Forty six male patients with chronic heart failure, aged 62 +/- 13 years, were studied. Their election fraction was less than 40% and their serum creatinine was less than 2 mg/dl. Serum uric acid and catecholamines, maximal oxygen consumption (VO2 max) and left ventricular ejection fraction were measured. Mortality and the need for cardiac transplant were recorded as endpoints during a mean follow up of 39 +/- 18 months. The relationship between basal measures and the occurrence of events was analyzed using univariate and multivariate methods. RESULTS: Basal VO2 max and left ventricular ejection fraction were 16 +/- 4.6 ml/kg/min and 22 +/- 7% respectively. Eighteen patients died and three required transplantation during the follow up. Patients reaching these endpoints had a lower VO2 max and left ventricular ejection fraction and higher uric acid levels. Multivariate analysis accepted left ventricular ejection fraction (relative risk 0.89, 95% CI 0.82-0.97) and serum uric acid (relative risk 1.335 95% CI 1.02-1.74) as significant predictors of events. The relative risk for cardiac transplantation was 7.07 times higher among those with a serum uric acid over 7 mg/dl. CONCLUSIONS: A high serum uric acid is an independent predictor of bad prognosis in patients with stable chronic heart failure.

Cavity solitons in two-level lasers with dense amplifying medium.

Local-field effects are known to induce bistability in dense optical media. We examine theoretically whether this property is preserved in broad-area cavities, and show that bistability between the homogeneous lasing and nonlasing states of the system persists provided a Fourier filtering technique is used to prevent off-axis emission. The resulting bistability gives rise to spatial light localization in the form of cavity solitons, which exhibit a particularly large degree of plasticity as a function of the characteristics of the addressing beam. This is the simplest laser able to sustain cavity solitons.

Trombosis en el infarto agudo del miocardio en hospitales chilenos: la experiencia del grupo GEMI / Thrombolysis in the acute myocardial infarction in chilean hospitals: the gemi group experience

Antecedentes: La trombolisis es uno de los métodos de reperfusión coronaria que permite reducir la mortalidad del infarto agudo del miocardio (IAM). Lamentablemente no todos los pacientes con indicación de trombolítico reciben el tratamiento. Objetivo: Evaluar los cambios en el empleo de trombolíticos a través del tiempo en pacientes con IAM y supradesnivel ST y analizar las variaciones en mortalidad según el período de registro. Método: Se compara la información de tres registros efectuados los años 93-95 (R1), 97-98 (R2), y los pacientes incluidos en el año 2001 del registro GEMI actualmente en curso (R3), en el que participan 23 hospitales de Santiago y regiones. Se recolecto información sobre latencia en administración del trombolítico, motivo de la no utilización y evolución intrahospitalaria de los pacientes que ingresaron con el diagnóstico de IAM Q o con supradesnivel ST (SDST). Resultados: En R1 se recolectaron 2.155 pacientes con IAM y SDST, en R2: 1.436 pacientes y en R3: 789 pacientes. El porcentaje que recibió trombolíticos fue de 37,8 por ciento, 41,4 por ciento y 45,1 por ciento, respectivamente. La mortalidad global en cada uno de los registros fue de R1: 11,2 por ciento, R2: 9,9 por ciento y R3: 8,9 por ciento ( p para tendencias: NS). Cuando se analiza según sexo, la mortalidad en hombres fue de 8,1 por ciento 7,4 por ciento y 7,1 por ciento (p para tendencias: NS). En mujeres estas proporciones fueron 23,6 por ciento 19,2 por ciento y 14,8 por ciento, respectivamente (p para tendencias: <0,05). El motivo de no uso trombolítico, dato consignado en R2 y R3, se debió a: ingreso tardío (45 por ciento y 38 por ciento respectivamente), contraindicación (9,5 y 12,5), no disponibilidad de él (1,5 por ciento y 0,23 por ciento). En el resto de los pacientes se consignó como “otro” el motivo de no uso. (De este análisis se excluyeron los pacientes sometidos a angioplastia primaria). Se observa un aumento en la proporción de pacientes sometidos a trombosis, asociado a una reducción en la mortalidad global en ellos. Conclusión: La reducción de la mortalidad en mujeres es determinante en la mejoría del pronóstico intrahospitalario en la población de trombolisados. Estos hallazgos pueden reflejar una mejor indicación y oportunidad del empleo de trombolíticos, así como de los fármacos de eficacia demostrada para el tratamiento de IAM con SDST...

Phase scaling properties of perturbation-induced multistability in a driven nonlinear system.

Phase scaling relations for the onsets of both saddle-node bifurcations and boundary crises induced by resonant periodic perturbations at subharmonic frequencies are found in a period-doubled system from the results of numerical simulation. These phase dependences determine the domains of existence of induced attractors in (bifurcation parameter, perturbation phase) parameter space. The overlapping of these domains leads to the formation of zones with different numbers of coexisting attractors. The numerical evidence was obtained on the basis of single-mode rate equations of a laser with parameters corresponding to a realistic loss-modulated CO2 laser.

Altered modulation of soluble guanylate cyclase by nitric oxide in patients with liver disease.

The glutamate-nitric oxide-cGMP pathway is impaired in brain in vivo in animal models of chronic moderate hyperammonemia either with or without liver failure. The impairment occurs at the level of activation of soluble guanylate cyclase by nitric oxide (NO). It has been suggested that the impairment of this pathway may be responsible for some of the neurological alterations found in hyperammonemia and hepatic encephalopathy. Soluble guanylate cyclase is also present in lymphocytes. Activation of guanylate cyclase by NO is also altered in lymphocytes from hyperammonemic rats or from rats with portacaval anastomosis. We assessed whether soluble guanylate cyclase activation was also altered in human patients with liver disease. We studied activation of soluble guanylate cyclase in lymphocytes from 77 patients with liver disease and 17 controls. The basal content of cGMP in lymphocytes was decreased both in patients with liver cirrhosis and in patients with chronic hepatitis. In contrast, cGMP concentration was increased in plasma from patients with liver disease. Activation of guanylate cyclase by NO was also altered in liver disease and was higher in lymphocytes from patients with cirrhosis or hepatitis than that in lymphocytes from controls. Successful treatment with interferon of patients with hepatitis C reversed all the above alterations. Altered modulation of soluble guanylate cyclase by NO in liver disease may play a role in the neurological and hemodynamic alterations in these patients.

Aluminium impairs the glutamate-nitric oxide-cGMP pathway in cultured neurons and in rat brain in vivo: molecular mechanisms and implications for neuropathology.

Aluminium (Al) is a neurotoxicant and appears as a possible etiological factor in Alzheimer's disease and other neurological disorders. The mechanisms of Al neurotoxicity are presently unclear but evidence has emerged suggesting that Al accumulation in the brain can alter neuronal signal transduction pathways associated with glutamate receptors. In cerebellar neurons in culture, long term-exposure to Al added 'in vitro' impaired the glutamate-nitric oxide (NO)-cyclic GMP (cGMP) pathway, reducing glutamate-induced activation of NO synthase and NO-induced activation of the cGMP generating enzyme, guanylate cyclase. Prenatal exposure to Al also affected strongly the function of the glutamate-NO-cGMP pathway. In cultured neurons from rats prenatally exposed to Al, we found reduced content of NO synthase and of guanylate cyclase, and a dramatic decrease in the ability of glutamate to increase cGMP formation. Activation of the glutamate-NO-cGMP pathway was also strongly impaired in cerebellum of rats chronically treated with Al, as assessed by in vivo brain microdialysis in freely moving rats. These findings suggest that the impairment of the Glu-NO-cGMP pathway in the brain may be responsible for some of the neurological alterations induced by Al.

Association of noninvasive markers of coronary artery reperfusion to assess microvascular obstruction in patients with acute myocardial infarction treated with primary angioplasty.

Early restoration of coronary artery patency through primary angioplasty limits infarct size and improves survival. Increasing evidence, however, suggests that microvascular obstruction is often present despite coronary artery recanalization. This may limit the benefits of reperfusion therapy. We studied the use of noninvasive markers of coronary artery reperfusion as indicators of microvascular obstruction and determinants of prognosis in 98 patients with acute myocardial infarction (AMI) who were successfully treated with primary angioplasty (Thrombolysis In Myocardial Infarction grade 3 flow and residual stenosis <30%). Plasma creatine kinase (CK) levels and 12-lead electrocardiograms were performed on admission, at 90 minutes, and at 6, 12, and 24 hours after treatment. We defined: (1) reperfusion as resolution of ST-segment elevation >50% at 90 minutes, with peak CK levels within 12 hours, and T-wave inversion within 24 hours; and (2) failed reperfusion, as the absence of these parameters. Of the 98 patients studied, 87 (88.8%) had reperfusion and 11 (11.2%) had failed reperfusion. Infarct location was anterior (versus inferior) in 9 patients in the failed reperfusion group (81.8%) compared with 41 patients in the reperfusion group (47.1%) (p <0.01). Congestive heart failure >24 hours after presentation or in-hospital death occurred in 11 patients (12.6%) in the reperfusion group versus 5 (45.5%) in the failed reperfusion group (p <0.01). One-year survival was 96.1% for the reperfusion group and 60.6% for the failed reperfusion group (p <0.0001). We conclude that the association of noninvasive markers of reperfusion better identifies patients with microvascular obstruction among those who had a "successful" primary angioplasty. Evidence of impaired microvascular reperfusion is associated with a poor in-hospital and 1-year outcome.

Altered content and modulation of soluble guanylate cyclase in the cerebellum of rats with portacaval anastomosis.

It is shown that the glutamate-NO-cGMP pathway is impaired in cerebellum of rats with portacaval anastomosis in vivo as assessed by in vivo brain microdialysis in freely moving rats. NMDA-induced increase in extracellular cGMP in the cerebellum was significantly reduced (by 27%) in rats with portacaval anastomosis. Activation of soluble guanylate cyclase by the NO-generating agent S-nitroso-N-acetyl-penicillamine and by the NO-independent activator YC-1 was also significantly reduced (by 35-40%), indicating that portacaval anastomosis leads to remarkable alterations in the modulation of guanylate cyclase in cerebellum. Moreover, the content of soluble guanylate cyclase was increased ca. two-fold in the cerebellum of rats with portacaval anastomosis. Activation of soluble guanylate cyclase by NO was higher in lymphocytes isolated from rats with portacaval anastomosis (3.3-fold) than in lymphocytes from control rats (2.1-fold). The results reported show that the content and modulation of soluble guanylate cyclase are altered in brain of rats with hepatic failure, resulting in altered function of the glutamate-NO-cGMP pathway in the rat in vivo. This may lead to alterations in cerebral processes such as intercellular communication, circadian rhythms, including the sleep-waking cycle, long-term potentiation, and some forms of learning and memory.

[Changes in the patterns of drug prescription for acute myocardial infarct. Comparison of 2 periods]. / Cambios en los patrones de prescripción de medicamentos en el infarto agudo del miocardio. Comparación de dos períodos.

BACKGROUND: Pharmacotherapy of Chilean patients with acute myocardial infarction has been recorded in 37 hospitals since 1993. AIM: To compare pharmacotherapy for acute myocardial infarction in the period 1993 to 1995 with the period 1997-1998. PATIENTS AND METHODS: Drug prescription during hospital stay was recorded in 2957 patients admitted to Chilean hospitals with an acute myocardial infarction in the period 1993-1995 and compared with that of 1981 subjects admitted in the period 1997-1998. RESULTS: When compared with the former period, in the lapse 1997-1998 there was an increase in the frequency of prescription of aspirin (93 and 96.1% respectively) beta blockers (37 and 55.2% respectively) and angiotensin converting enzyme inhibitors (32 and 53%). The prescription of thrombolytic therapy did not change (33 and 33.7% respectively). There was a reduction in the prescription of calcium antagonists and antiarrhythmic drugs. CONCLUSIONS: During the period 1997-1998, the prescription of drugs with a potential to reduce the mortality of acute myocardial infarction, increased. The diffusion of guidelines for the management of this disease may have influenced this change.

[Hyperuricemia as a marker for anaerobic threshold in chronic cardiac failure]. / La hiperuricemia es un marcador del umbral anaeróbico en la insuficiencia cardíaca crónica.

BACKGROUND: Patients with chronic cardiac failure often have elevated plasma uric acid levels, that are associated to a dismal prognosis. AIM: To investigate possible metabolic mechanisms to explain elevated uric acid levels in these patients. PATIENTS AND METHODS: Eighteen patients with chronic cardiac failure aged 61 +/- 10 years old, without gout or renal failure and not using high doses of diuretics (equal or less than 80 mg/day furosemide or 50 mg/day hydrochlorothiazide) were studied. Plasma uric acid levels were correlated with anaerobic threshold, maximal oxygen uptake, plasma noradrenaline and creatinine and left ventricular ejection fraction, measured radioisotopically. RESULTS: Mean maximal oxygen uptake was 16.6 +/- 4.2 ml/kg/min. There was a negative correlation between uric acid levels and maximal oxygen uptake or maximal oxygen uptake/body surface area (r = 0.521 and -0.533 respectively, p < 0.05). Patients with uric acid levels over 7 mg/dl had a lower anaerobic threshold than patients with lower levels (9.81 +/- 2.41 and 13.08 +/- 3.28 ml/kg/min respectively, p < 0.05). No significant differences in maximal oxygen uptake were observed in these two groups of patients (15.5 +/- 4.24 and 18.08 +/- 3.86 ml/kg/min respectively). Uric acid levels did not correlate with plasma noradrenaline, creatinine or left ventricular ejection fraction. CONCLUSIONS: These results suggest that a defect in cellular oxygenation contributes to the elevation of plasma uric acid levels in patients with chronic cardiac failure.

[Selective training of respiratory muscles in patients with chronic heart failure]. / Entrenamiento selectivo de los músculos respiratorios en pacientes con insuficiencia cardíaca crónica.

BACKGROUND: Patients with chronic heart failure have a lower inspiratory muscle strength and fatigue endurance. AIM: To assess the effects of selective training of respiratory muscles in patients with heart failure. PATIENTS AND METHODS: Twenty patients with stable chronic heart failure, aged 58.3 +/- 3 years with an ejection fraction of 28 +/- 9%, were subjected to respiratory muscle training with threshold valves. The load was fixed in 30% of maximal inspiratory pressure (PImax) in 11 and in 10% of PImax in nine. Two sessions of 15 minutes, 6 days per week, during 6 weeks were done. Degree of dyspnea (Mahler score), maximal oxygen uptake, distance walked in 6 minutes, respiratory muscle function and left ventricular ejection fraction were measured before and after training. RESULTS: Both training loads were associated to an improvement in dyspnea (+2.7 +/- 1.8 and +2.8 +/- 1.8 score points with 30% PImax and 10% PImax respectively), maximal oxygen uptake (from 19 +/- 3 to 21.6 +/- 5 and from 16 +/- 5 to 18.6 +/- 7 ml/kg/min with 30% PImax and 10% PImax respectively, p < 0.05), PImax (from 78 +/- 22 to 99 +/- 22 and from 72 +/- 34 to 82.3 cm H20 with 30% PImax and 10% PImax respectively), sustained PImax (from 63 +/- 18 to 90 +/- 22 and from 58 +/- 3 to 69 +/- 3 cm H20 with 30% PImax and 10% PImax respectively), and maximal sustained load (from 120 +/- 67 to 195 +/- 47 and from 139 +/- 120 to 192 +/- 154 g with 30% PImax and 10% PImax respectively). The distance walked in 6 min only increased in subjects trained at 30% PImax (from 451 +/- 78 to 486 +/- 68 m). CONCLUSIONS: Selective training of respiratory muscles results in a functional improvement of patients with chronic heart failure.

Variation in patient management and outcomes for acute coronary syndromes in Latin America and North America: results from the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial.

BACKGROUND: Although more than 9500 patients have been enrolled in major clinical trials in Latin America, practice patterns in this region have rarely been examined. We sought to compare characteristics, resource utilization, and outcomes of patients treated for acute coronary syndromes in Latin America with those in North America. METHODS: The Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Theraphy Trial (PURSUIT) enrolled 10,948 patients with non-ST-segment elevation acute coronary syndromes, including 585 in Latin America and 4358 in North America. We analyzed regional differences in patient groups, treatment patterns, and outcomes and used logistic regression analysis to identify association of enrollment region and survival. RESULTS: For patients in Latin America, the length of hospital stay was significantly longer (10 [7, 15] days vs 6 [4, 9], P <.001). Angiograms, angioplasty, and bypass surgery were significantly less common in Latin America (46.2%, 17.6%, and 11.3% vs 79.4%, 33.6%, and 19.4%, P <.001). Thirty-day death/myocardial infarction was not significantly higher, although mortality alone was significantly higher (6.8% vs 3.1%, P <.001). After adjustment for baseline characteristics, enrollment in Latin America remained an independent predictor for death at 30 days (odds ratio [OR] [95% confidence interval (CI)] 2.42 [1.60-3.67]) and persisted at 6 months (OR [95% CI] 2.5 [1.8-3.4]). CONCLUSIONS: Latin American patients treated for acute coronary syndromes were managed less invasively and were twice as likely as their North American counterparts to die within 6 months. This mortality difference was not explained by imbalances in baseline risk.

Role of nitric oxide and cyclic GMP in glutamate-induced neuronal death.

Glutamate is the main excitatory neurotransmitter in mammals. However, excessive activation of glutamate receptors is neurotoxic, leading to neuronal degeneration and death. In many systems, including primary cultures of cerebellar neurons, glutamate neurotoxicity is mainly mediated by excessive activation of NMDA receptors, leading to increased intracellular calcium which binds to calmodulin and activates neuronal nitric oxide synthase (NOS), increasing nitric oxide (NO) which in turn activates guanylate cyclase and increases cGMP. Inhibition of NOS prevents glutamate neurotoxicity, indicating that NO mediates glutamate-induced neuronal death in this system. NO generating agents such as SNAP also induce neuronal death. Compounds that can act as "scavengers" of NO such as Croman 6 (CR-6) prevent glutamate neurotoxicity. The role of cGMP in the mediation of glutamate neurotoxicity remains controversial. Some reports indicate that cGMP mediates glutamate neurotoxicity while others indicate that cGMP is neuroprotective. We have studied the role of cGMP in the mediation of glutamate and NO neurotoxicity in cerebellar neurons. Inhibition of soluble guanylate cyclase prevents glutamate and NO neurotoxicity. There is a good correlation between inhibition of cGMP formation and neuroprotection. Moreover 8-Br-cGMP, a cell permeable analog of cGMP, induced neuronal death. These results indicate that increased intracellular cGMP is involved in the mechanism of neurotoxicity. Inhibitors of phosphodiesterase increased extracellular but not intracellular cGMP and prevented glutamate neurotoxicity. Addition of cGMP to the medium also prevented glutamate neurotoxicity. These results are compatible with a neurotoxic effect of increased intracellular cGMP and a neuroprotective effect of increased extracellular cGMP.

Amplification of near-resonant signals via stochastic resonance in a chaotic CO2 laser

We show experimentally and numerically that a chaotic CO2 laser with modulated losses operating in the region of an intermittency resulting from the band-merging crisis can serve as an amplifier of near-resonant signals, i.e., signals with a frequency close to the first subharmonic frequency, via deterministic stochastic resonance. The mechanism underlying stochastic resonance in this case is a synchronization of the random switching events between two chaotic repellers after the band-merging crisis with near-resonant signals at the detuning frequency. We demonstrate experimentally that the gain factor in chaos is larger than near the first period-doubling bifurcation by a factor of 2. Numerical results obtained in a two-level rate-equation model are in good agreement with the experimental ones.

[Infective endocarditis: short and long-term results in 261 cases managed by a multidisciplinary approach]. / Endocarditis infecciosa: análisis de 261 casos y resultados del tratamiento con un enfoque multidisciplinario.

BACKGROUND: Early diagnosis, an effective treatment and prompt recognition of complications are essential to improve the prognosis of infective endocarditis (IE). AIM: To report the results of a multidisciplinary approach to diagnosis and management of patients with IE at the Universidad Católica de Chile Hospital. PATIENTS AND METHODS: The clinical history, diagnosis, treatment and outcome of 261 episodes (Duke criteria) of IE admitted between January 1980 and January 1999 were analyzed. These included 185 episodes of native, 73 of prosthetic valve and 3 of nonvalvular IE. RESULTS: Sixty nine percent of patients were men and the mean age was 49 +/- 16 years. Seventy five percent had a definite diagnosis of IE (Duke). S. viridans, staphylococci and enterococci together constituted 85% of the isolated bacterial strains. Twenty seven had culture-negative IE, related to a high incidence of antibiotic therapy prior to diagnosis. Transesophageal echocardiography was performed in 102 cases and it detected vegetations in 91% of aortic and 96% of mitral IE, rupture or prosthesis dehiscence in 67% of aortic and 52% of mitral IE and abscesses in 51% of aortic and 15% of mitral IE. Fifty one percent developed heart failure and 34% had embolic events. S. aureus IE was associated to a higher incidence of embolic events, complications which contraindicated surgery and increased mortality rate (27%). Of all patients, 40% were treated exclusively with antibiotics, 52% were operated on and 8% had surgical indication but were nonoperable because of serious complications. The overall mortality was 16.3%: 13% in the medical, 9% in the surgical and 81% in the non-operable groups. The type of treatment and mortality rates did not differ between IE of native valves and prosthetic valves. Long term follow up showed survival rates of 73% at 5 years and 66% at 10 years. CONCLUSION: A multidisciplinary approach may be very helpful to improve the prognosis of IE.

The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making.

CONTEXT: Patients with unstable angina/non-ST-segment elevation myocardial infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and cardiac ischemic events. OBJECTIVE: To develop a simple risk score that has broad applicability, is easily calculated at patient presentation, does not require a computer, and identifies patients with different responses to treatments for UA/NSTEMI. DESIGN, SETTING, AND PATIENTS: Two phase 3, international, randomized, double-blind trials (the Thrombolysis in Myocardial Infarction [TIMI] 11B trial [August 1996-March 1998] and the Efficacy and Safety of Subcutaneous Enoxaparin in Unstable Angina and Non-Q-Wave MI trial [ESSENCE; October 1994-May 1996]). A total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated heparin (test cohort) and 1953 to receive enoxaparin in TIMI 11B; 1564 and 1607 were assigned respectively in ESSENCE. The 3 validation cohorts were the unfractionated heparin group from ESSENCE and both enoxaparin groups. MAIN OUTCOME MEASURES: The TIMI risk score was derived in the test cohort by selection of independent prognostic variables using multivariate logistic regression, assignment of value of 1 when a factor was present and 0 when it was absent, and summing the number of factors present to categorize patients into risk strata. Relative differences in response to therapeutic interventions were determined by comparing the slopes of the rates of events with increasing score in treatment groups and by testing for an interaction between risk score and treatment. Outcomes were TIMI risk score for developing at least 1 component of the primary end point (all-cause mortality, new or recurrent MI, or severe recurrent ischemia requiring urgent revascularization) through 14 days after randomization. RESULTS: The 7 TIMI risk score predictor variables were age 65 years or older, at least 3 risk factors for coronary artery disease, prior coronary stenosis of 50% or more, ST-segment deviation on electrocardiogram at presentation, at least 2 anginal events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum cardiac markers. Event rates increased significantly as the TIMI risk score increased in the test cohort in TIMI 11B: 4.7% for a score of 0/1; 8.3% for 2; 13. 2% for 3; 19.9% for 4; 26.2% for 5; and 40.9% for 6/7 (P<.001 by chi(2) for trend). The pattern of increasing event rates with increasing TIMI risk score was confirmed in all 3 validation groups (P<.001). The slope of the increase in event rates with increasing numbers of risk factors was significantly lower in the enoxaparin groups in both TIMI 11B (P =.01) and ESSENCE (P =.03) and there was a significant interaction between TIMI risk score and treatment (P =. 02). CONCLUSIONS: In patients with UA/NSTEMI, the TIMI risk score is a simple prognostication scheme that categorizes a patient's risk of death and ischemic events and provides a basis for therapeutic decision making. JAMA. 2000;284:835-842