Epidemiologic variables and outcome of 1972 young patients with acute myocardial infarction. Data from the GISSI-2 database. Investigators of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2).

BACKGROUND: Acute myocardial infarction in younger patients is uncommon, occurring mainly in men. The recent introduction of thrombolysis improved survival, left ventricular function, and infarct size. OBJECTIVE: To evaluate characteristics and clinical outcome of the patients younger than 50 years randomized in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico study. All patients received a thrombolytic treatment. METHODS: The 11483 patients were divided into 3 age subgroups: younger than 50 years (17.2%), between 50 and 70 years (60.2%), and older than 70 years (22.6%). All relations between variables were first determined by an unadjusted analysis. An adjusted analysis was performed by multiple logistic regression models for in-hospital and 6-month mortality. RESULTS: While older patients had a significantly higher rate of a history of hypercholesterolemia, diabetes, and hypertension, smoking and a positive family history were significantly more frequent in younger patients. Total in-hospital and 6-month mortality were significantly lower in patients younger than 50 years (2.7% and 1.2%, respectively) than in patients between 50 and 70 years old (6.9% and 2.7%) and those older than 70 years (21.1% and 8.4%). After multivariate analysis, the predictive value of age was confirmed. CONCLUSIONS: Our findings, based on a large group of patients who received thrombolytic treatment, suggest that younger age is a significant independent indicator of a favorable prognosis after acute myocardial infarction.

Neurogenic pulmonary edema and variations of hemodynamic volumetric parameters in children following head trauma.

BACKGROUND: Currently there is no clear evidence of how changes in hemodynamic parameters are involved in the onset of neurogenic pulmonary edema. Aim of the study has been to correlate the principal variations of the intracranial pressure and volumetric hemodynamic parameters with the variations of extravascular lung water following severe head trauma in children. METHODS: We studied 28 children, 16 males and 12 females, mean ± SD age 71±29 months (range 24-130 months), admitted for traumatic head injury with Glasgow Coma scale ≤8. All patients received volumetric hemodynamic, and intracranial pressure monitoring following initial resuscitation and every four hours thereafter or whenever a hemodynamic deterioration was suspected. All readings were divided in 2 groups: with intracranial pressure (ICP) >15 mmHg or ≤15 mmHg. RESULTS: During the cumulative in hospital stay a total 508 sets of measurements were done. In the group with ICP >15 mmHg vs. that with ICP ≤15 mmHg we observed increased Extravascular Lung Water Index (EVLWi) (11.05±2.28 vs. 6.96±0.87 P<0.0001) and pulmonary permeability (8.50±1.19 vs. 5.08±0.90, P<0.0001), and decreased systemic vascular resistances, (1,451±371 vs. 1,602±447 P<0.0001) cerebral perfusion (48.87±18.67 vs. 69.72±11.36 P<0.0001) and PaO2/FiO2 ratio (349±122 vs. 490±96 P<0.0001). There was a significant correlation between EVLWi and pulmonary permeability (R2=0.83, P<0.0001). Fluid overload and cardiac functional index did not change significantly. CONCLUSION: The increased EVLWi observed in children following severe head trauma seems mainly related with pulmonary vascular permeability which is significantly increased when ICP is >15 mmHg.

Echocardiographic evaluation and clinical management of ductal shunting in hemodynamically unstable preterm neonates without congenital heart disease in the pediatric intensive care unit.

Although significant steps have been taken to monitor complex hemodynamics in neonatal and pediatric intensive care units, cardiovascular function in neonates is still evaluated by measuring blood pressure, heart rate, diuresis, central venous pressure (if a central venous catheter was placed), capillary refill time and oxygen saturation measurement in the upper and lower extremities. The use of other non-invasive or invasive technologies (for example, continuous impedance cardiography, transesophageal Doppler and continuous pulse contour methods) is, in fact, quite problematic in neonates in whom relevant hemodynamic changes are common during the transition to postnatal life. For these reasons, use of transthoracic echocardiography, performed by skilled pediatric intensivists, is increasing in several dedicated centers to guide treatment choices in hemodynamically unstable neonates.

Estimates of lifetime attributable risk of cancer after a single radiation exposure from 64-slice computed tomographic coronary angiography.

AIMS: To estimate the life attributable risk (LAR) of cancer incidence over a wide range of dose radiation exposure and a large spectrum of possible diagnostic computed tomographic coronary angiography (CTCA) scenarios. METHODS: This study included 561 consecutive patients who underwent a successful prospective ECG-gating CTCA protocol (low-dose group) 64-slice CTCA and 188 patients who underwent retrospective ECG-gating CTCA with ECG-triggered dose modulation CTCA (high-dose group). LAR was computed, given the organ equivalent dose, for all cancers in both sexes. LAR was tabulated for each decile of dose-length product by 10-year age classes, separately for each sex. RESULTS: Estimates of LAR of any cancer for an exposure at age < or =40 year were lower in males than in females for any given quantile. At age >/ or =50 years, LAR was similar between sexes only at the lowest exposure doses, whereas at higher dosage, it was, in general, higher for women. At the median age of this case series (62 years) and for a radiation exposure ranging from 1.33 to 3.81 mSv, LAR was 1 in 4329 (or 23.1 per 10(5) persons exposed) and 1 in 4629 (or 21.6 per 10(5) persons) in men and women, respectively. For an exposure ranging from 10.34 to 18.97 mSv at the same median age, the LAR of cancer incidence was 1 in 1336 (or 74.8 per 10(5) persons) in men and doubled (1 in 614 or 162.8 per 10(5) persons) in women. CONCLUSIONS: This study provided an estimate of the LAR of cancer in middle-aged patients of both sexes after a single diagnostic CTCA, providing an easy-to-read table.

Relation between coronary atherosclerotic plaques and traditional risk factors in people with no history of cardiovascular disease undergoing multi-detector computed coronary angiography.

AIMS: To prospectively investigate the prevalence of coronary artery plaques (CAP) as detected by computed tomography-based angiography in a large number of consecutive individuals with no history of coronary artery disease (CAD) or acute coronary syndrome; to evaluate whether traditional risk factors are related to prevalence of CAP and to the expected 10-year risk of first major or fatal cardiovascular event (CVE). DESIGN: Prospective, single-centre, cross-sectional study. SETTING: The division of Cardiology at Fondazione Cardiocentro Ticino Lugano, Switzerland. METHODS: We prospectively included 920 consecutive individuals with no history of CAD who underwent computed tomography coronary angiography (CTCA). Risk estimation of fatal and non-fatal CVE was assessed using Global Assessment Risk (GAR) and Systematic Coronary Risk Evaluation (SCORE), respectively. Logistic regression was used to assess the association of risk factors with the prevalence of CAP. RESULTS: CAP was found in 459 (49.9%) individuals. Older age, higher body mass index, male gender, diabetes, hypertension and dyslipidaemia all increased the likelihood of the CAP burden at univariable analysis (p<0.001). At the multivariable analysis older age, male gender, hypertension and diabetes independently increased the likelihood of CAP burden (p<0.001). An increase in likelihood of CAP was observed in the presence of one, two and three or more risk factors and with an increasing value of GAR and SCORE. Notably, about 18% of subjects with CAP did not report any traditional risk factors and among individuals without CAPs, 12% had three or more risk factors. CONCLUSIONS: A direct relation between the prevalence of CAP, number of risk factors and the related 10-year risk of CVE was found. 18% of subjects without risk factors had CAP. In these individuals CTCA may help in further optimising the risk reduction strategies on an individual basis.

[Time loss in the therapy of acute heart infarct]. / Zeitverlust in der Therapie des akuten Herzinfarkts.

As part of the ISIS study, the prehospitalization phase in 570 patients with acute myocardial infarction was evaluated and protocolled in 34 Swiss hospitals. The aim was to assess whether the time lapse between onset of pain symptoms and start of treatment could be shortened. It was felt that, particularly in the case of lethal cardiac arrhythmias, rapid intervention could secure reversal or controlled relief of symptoms and/or conduction disorders. The study protocol recorded the specific time lapses between onset of symptoms and notification of the physician, notification of the physician and hospital admission, and between hospital admission and therapeutic action. The longest time lapse observed was the patient's delay (57%). Delay by the patient was shortened when pain symptoms (a) occurred during daytime, (b) were preceded by symptoms in the week before the infarction, (c) occurred at work, and (d) occurred during exercise, particularly in the company of unknown persons. The longest time lapse observed in hospital was associated with the night shift. The time lost through delay in contacting a doctor, the main factor in delaying therapeutic action in acute myocardial infarction, is very difficult to influence since the target group for a public information campaign is hard to identify. On the other hand, the "door to needle" time lapse observed in hospital can be reduced by the introduction of clear-cut guidelines.

Successful weaning from cardiopulmonary bypass with central venous prostaglandin E1 and left atrial norepinephrine infusion in patients with acute pulmonary hypertension.

OBJECTIVE: Postoperative pulmonary hypertension increases the mortality risk in cardiac surgery. We have used central venous prostaglandin E1 (PGE1) and left atrial norepinephrine (NE) infusion to wean from cardiopulmonary bypass (CPB) patients with refractory postoperative pulmonary hypertension. DESIGN: Observational, nonrandomized study. SETTING: Department of Cardiac Surgery in a university hospital. PATIENTS: We studied 10 nonconsecutive American Society of Anesthesiologists III and New York Heart Association class III-IV patients with postoperative pulmonary hypertension and low cardiac output syndrome preventing separation from CPB. INTERVENTIONS: Patients received right atrial PGE1 (31.5 +/- 6.26 ng/kg/min) and left atrial NE (0.11 +/- 0.02 microg/kg/min) infusion. Hemodynamic data were obtained before CPB (T0), after CPB under maximal inotropes and vasodilator infusion (T1), 10 mins (T2) and 12 hrs (T3) after PGE1 and NE infusion, and 48 hrs after withdrawal of PGE1 and NE (T4). MEASUREMENTS AND MAIN RESULTS: All patients were successfully weaned from CPB and survived. The biatrial infusion of PGE1 and NE caused a dramatic reduction in mean pulmonary artery pressure (from 42.8 +/- 5.1 mm Hg at T1 to 28.5 +/- 2.6 mm Hg at T2 and 20.5 +/- 2.0 mm Hg at T4), pulmonary vascular resistance index (from 1158 +/- 269 dyne x sec/cm5 x m2 at T1 to 501 +/- 99 dyne x sec/cm5 x m2 at T2 and 246 +/- 50 dyne x sec/cm5 x m2 at T4), and pulmonary-to-systemic vascular resistance index ratio (from 0.61 +/- 0.17 at T1 to 0.20 +/- 0.04 at T2 and 0.11 +/- 0.03 at T4). Cardiac index increased from 1.7 +/- 0.2 L/min/m2 at T1 to 2.3 +/- 0.2 L/min/m2 at T2 and 2.9 +/- 0.1 L/min/m2 at T4. CONCLUSIONS: In patients with refractory postoperative pulmonary hypertension, the combined administration of low-dose PGE1 in the right atrium and NE in the left atrium is an effective means to wean patients from cardiopulmonary bypass.

Central venous catheterization in pediatric patients affected by hematological malignancies.

The objective of this retrospective study was to evaluate the significance and complications of percutaneous central venous catheterization in pediatric patients affected by hematologic malignancies. One hundred and fifty-eight central venous catheters were inserted in 125 pediatric patients (male/female 67/58; median age: 4 years; range 10 m - 6 y.) affected by hematological malignancies. Venous access was obtained by means of a tunnelled silicone rubber Groshong catheter inserted percutaneously in the subclavian vein (91.1%), the internal jugular vein or in the femoral vein. The medial duration of catheterization was 231.8 days (range 8-1014 days). The total number of catheter days was 33,792 (92.6 years). There were no complications related to catheter insertion. Only one patient developed significant post-operative bleeding. One hundred and nine catheters (68.9%) were removed when they were no longer needed and 49 (31.1%) were removed due to complications: 6 catheter occlusions (12.2%), 7 were accidentally withdrawn (14.3%), 3 for local infections (6.1%) and 33 for catheter-related infection (67.3%). A Groshong catheter seems to provide good access to the blood stream for a long period of time with a low incidence of complications in children with acute hematological malignancies.

Low dose remifentanyl infusion for analgesia and sedation in ventilated newborns.

AIM: The aim of this study was to evaluate the analgesic effects of remifentanyl on mechanically ventilated newborns. METHODS: Eighteen newborns, mechanically ventilated, were submitted to continuous infusion of R. A pain scale was used to evaluate comfort during mechanical ventilation. Data were collected at T0, T1, Tn, T ext, T post-ext; statistical analysis was performed by Student's t test and Pearson coefficient. RESULTS: Mean R infusion time was 66.94+/-22.24 h, with mean dose of R 0.146+/-0.038 gamma/kg/min. Mean time to reach comfort was 20+/-13.11 h with a mean infusion of R equal to 0.173+/-0.146 gamma/kg/min; R was 0.18+/-0.039 gamma/kg/min on pressure controlled ventilation and R was 0.09+/- 0.045 gamma/kg/min on assisted ventilation. Statistically significant was considered the decrease in HR as well as the increase of SpO2 at T0 vs 30 min after infusion. CONCLUSION: No adverse effects were observed during and after infusion.

The effect of the gastrointestinal lipase inhibitor, orlistat, on serum lipids and lipoproteins in patients with primary hyperlipidaemia.

The effect of orlistat, a nonabsorbed inhibitor of gastric and pancreatic lipases, was examined in patients with primary hyperlipidaemia (serum cholesterol > or = 6.2 mmol.l-1 and triglycerides < or = 5.0 mmol.l-1) not responsive to dietary change alone. In a multicentre, randomised, double-blind study, 103 men and 70 women received 30, 90, 180, or 360 mg or orlistat or placebo for 8 weeks. Total and low-density lipoprotein cholesterol levels were reduced by 4% and 5% with 30 mg orlistat, by 7% and 8% with 90 mg orlistat, by 7% and 7% with 180 mg orlistat and by 11% and 10% with 360 mg orlistat compared to placebo. High density lipoprotein cholesterol levels significantly decreased in the 360 mg orlistat group. Triglyceride levels significantly increased in the placebo group but not in the drug groups. Body weight decreased by 1.2 kg with 360 mg orlistat, despite a weight maintenance diet. Decreases in vitamin E and D levels occurred, although both vitamins remained within the normal range. Adverse effects from the gastrointestinal tract were frequent, but led to discontinuation of therapy in only seven patients. Orlistat is a new therapeutic drug for the treatment of hyperlipidaemia that may be particularly useful among overweight patients. Its potential place in therapy will await long-term studies. Vitamin supplementation should be considered during treatment.

Monitoring of intrathoracic volemia and cardiac output in critically ill children.

AIM: Hemodynamic monitoring is an important step in the management of critically ill children despite the difficulty in measuring preload indices continuously. The aim of the study was to analyze cardiac output parameters and preload indices after acute changes in mean airway pressure and volemia. METHODS: Twenty-three children treated at our unit were enrolled in a prospective non randomized cohort study. Respiration was supported by controlled mechanical ventilation with positive expiratory-end pressure (PEEP), peak inspiratory pressure <20 cm H(2)O and mean airway pressure <10 cm H(2)O, and hemodynamic monitoring using the PiCCO system. Hemodynamic parameters were measured at T0 (base line), T(1) (after an increase in PEEP of 5 cm H(2)O for 10 min), and T(2) (after fluid challenge). The statistical analysis (BMPD New System software package) comprised comparison of changes at T(0) vs T(1), T(1) vs T(2) and T(0) vs T(2), construction of 3 correlation matrices and multiple linear regression analysis. RESULTS: Sixty-nine hemodynamic parameters were measured in the 23 patients. A comparison between T(0) and T(1) showed no significant changes; differences between T(0) and T(2) were found for cardiac index (CI), (p=0.003); between T(0) and T(2) significant differences were found for CI (p=0.0015), intrathoracic blood volume index (ITBVI) (p=0.04) and stroke volume index (SVI) (p=0.06). The analysis of the correlation matrices yielded ITBVI with CI (p=0.0006), ITBVI with SVI (p=1 x 10(-5)), CI with SVI (p=0.002); a significant correlation between CI and extravascular lung water index (EVLWI) was found only at T(1). Multiple linear regression analysis showed that ITBVI and SVI were predictive for variance of CI at each time point. CONCLUSION: ITBVI measured by a volumetric monitoring system such as the PiCCO may be considered a sensitive preload indicator also in critically ill children.

[Pravastatin in the treatment of primary hypercholesterolemia: a Swiss multicenter study]. / Pravastatin zur Behandlung der primären Hypercholesterinämie: Schweizer Multizenter-Studie.

Conventional lipid-lowering agents displayed only limited efficacy in lowering total and LDL cholesterol and a high incidence of side effects. Pravastatin is a new potent cholesterol-lowering agent, which selectively inhibits hepatic HMG-CoA-reductase. In a double-blind, placebo-controlled Swiss multicenter study with determination of lipids and lipoprotein in a central laboratory, the efficacy and safety of 6 months' therapy with pravastatin was evaluated in 50 patients with mild hypercholesterolemia and additional coronary risk factors. Compared to baseline and after 26 weeks' therapy, pravastatin significantly reduced total cholesterol (pravastatin vs placebo, -17% vs +7%, p < 0.0001) and LDL cholesterol (-26 vs +2%, p < 0.0001). The total/HDL cholesterol ratio ( = "atherogenic index") was comparable in the two groups at baseline (5.9 +/- 1.1 vs 6.3 +/- 0.9), and was distinctly lowered by pravastatin but not placebo (-20 vs 0%, p < 0.0001). In 11 patients in whom the reduction of serum total cholesterol after 13 weeks' treatment with 20 mg pravastatin was still below target (on average -9.1%), doubling of the dose produced a further decrease of 4.3%. Serum HDL cholesterol and serum triglyceride levels did not change significantly during pravastatin treatment as compared to baseline and placebo. Pravastatin was well tolerated during the 26 weeks without relevant subjective side-effects. There were 5 dropouts during the study, 2 patients in the pravastatin group and 3 in the placebo group. These findings document that pravastatin, administered in a single daily dose of 20 to 40 mg, effectively lowers serum cholesterol and total-/HDL-cholesterol improving action and is well tolerated.

Within-patient variability of hormone and cytokine concentrations in heart failure.

Several studies on disease and treatment effects on neurohormones have been conducted with small numbers of patients, using one blood sample as representative of their states. The aim of this study was to assess the within-patient variability of plasma concentrations of several hormones and cytokines of recent interest, in patients with moderate heart failure and controlled stable background therapy over 3 weeks. Blood for neurohormone and cytokine assays was sampled in duplicate from 18 patients with moderate heart failure. After an initial visit, the patients were kept on stable therapy until the second blood sampling 21 +/- 3 days later. The plasma concentrations of several neurohormones (endothelin, renin, angiotensin II, aldosterone, norepinephrine) and cytokines (interleukin-6 (IL-6), interleukin-13 (IL-13), ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF) and soluble receptor type I of tumour necrosis factor-alpha, (sTNF-RI) were measured with immunochemical methods. Some cytokines (IL-13, CNTF and LIF) were not detected. Despite clinically satisfactory ACE inhibition, circulating angiotensin II and aldosterone levels were still elevated in some patients, suggesting aldosterone escape. The between-visit agreement of plasma concentrations measured in duplicate was less than 35% for all circulating factors, except renin which showed a higher variability throughout the 3-week study period.

Evaluación no invasiva del status volémico. Confrontación entre indicadores radiográficos y volumétricos / Not invasive evaluation of the status volémico. Confrontation between warning radiográficos and volumetric

La finalidad de nuestro estudio ha sido la de evaluar la existencia de posibles correlaciones entre los principales indicadores volumétricos de carga previa y de función cardiaca, obtenida mediante el sistema PiCCO® (Pulsion Medical Systems, Munich, Alemania), con todos los datos derivados del análisis sistemático de la radiografía de tórax en proyección antero posterior, así como el pedúnculo vascular (VPW) y el índice cardiotorácico (RCT). Materiales y Métodos: Hemos incluido 15 pacientes y analizado conjuntamente 79 radiografías de pacientes electivos. Todos fueron sometidos a monitorización hemodinámica mediante PiCCO y al estudio de los parámetros radiográficos obtenidos (VPW, RCT). El análisis: cálculo de la media y desviación estándar; un análisis de la correlación para las siguientes parejas de parámetros: volumen de sangre intratorácica (ITBVI)-RCT, ITBVI-VPW, agua extravascular (EVLWI )-RCT, EVLWI-VPW . Resultados. Las parejas de los valores estudiados han evidenciado una correlación linear con R igual a 0.54 entre EVLWI-RCT. Discusión. Aunque es un estudio preliminar, los hallazgos más significativos se ven en las variaciones de RCT, que presentan una correspondencia con el edema intersticial antes de que aparezca un incremento crítico de la rata de líquido alveolar. En nuestra experiencia no hemos evidenciado una fuerte correlación entre VPW y los normales indicadores volumétricos de precarga. De acuerdo con los datos en literatura y también en la experiencia pediátrica, estos instrumentos presentan límites que aún no consienten sustituir completamente a la correcta cuantificación de la rata de agua extravascular, en respuesta al incremento volémico. Palabras Claves: Monitorización Hemodinámica, Monitor de PiCCO, Volemia, pedúnculo vascular, índice cardiotorácico, Volumen de sangre intratorácica, Volumen de agua extravascular intrapulmonar, Índice de función cardiaca...