[Acute coronary syndrome complicated by heart failure as predictor of long-term infarction]. / Insuficiencia cardiaca en el seno de un síndrome coronario agudo como predictor de infarto a largo plazo.

BACKGROUND: Heart failure (Killip>I) in patients with acute coronary syndrome (ACS) is a recognized risk factor for death. However, its relationship with the risk of new acute ischemic events has not been well established. OBJECTIVE: The aim of this study has been to evaluate the association between Killip>I on admission and the risk of a new acute myocardial infarction (AMI) during follow-up due to ACS. PATIENTS AND METHODS: A total of 972 and 426 survivors of an ACS with non-ST segment evaluation (Non-STE-ACS) and AMI with ST segment elevation (STEMI) were studied prospectively and consecutively. The presence of Killip>I was determined on admission together with the classical prognostic variables. The relationship between Killip>I and subsequent post-discharge AMI was established with the Cox regression adapted for competitive events. RESULTS: During a median follow-up of 3 years, 135 (13.9%) and 53 (12.4%) patients with Non-STE-ACS and STEMI presented a new AMI. Patients with Non-STE-ACS and STEMI with Killip>I (15.6% and 21.3% respectively) showed a higher incidence of AMI (28.3 vs 6.3 and 10.6 vs 3.3 per 100 patients-years of follow-up, p<0.001, respectively). In the multivariate analysis, adjusted for traditional risk factors and controlled for competitive events (death and revascularization), confirmed that Killip>I subjects with Non-STE-ACS and STEMI showed a significantly higher risk of AMI (HR: 1.76; CI 95%: 1.15-2.68; p=0.009 and HR: 1.90; 95% CI: 1.07-3.36; p=0.029 respectively). CONCLUSIONS: In patients with Non-STE-ACS and STEMI, the presence of Killip>I on admission is independently associated to an increased risk of long-term AMI.

Selection for thermostability can lead to the emergence of mutational robustness in an RNA virus.

Mutational robustness has important evolutionary implications, yet the mechanisms leading to its emergence remain poorly understood. One possibility is selection acting on a correlated trait, as for instance thermostability (plastogenetic congruence). Here, we examine the correlation between mutational robustness and thermostability in experimental populations of the RNA bacteriophage Qß. Thermostable viruses evolved after only six serial passages in the presence of heat shocks, and genome sequencing suggested that thermostability can be conferred by several alternative mutations. To test whether thermostable viruses have increased mutational robustness, we performed additional passages in the presence of nitrous acid. Whereas in control lines this treatment produced the expected reduction in growth rate caused by the accumulation of deleterious mutations, thermostable viruses showed no such reduction, indicating that they are more resistant to mutagenesis. Our results suggest that selection for thermostability can lead to the emergence of mutational robustness driven by plastogenetic congruence. As temperature is a widespread selective pressure in nature, the mechanism described here may be relevant to the evolution of mutational robustness.

A genetic background with low mutational robustness is associated with increased adaptability to a novel host in an RNA virus.

Although mutational robustness is central to many evolutionary processes, its relationship to evolvability remains poorly understood and has been very rarely tested experimentally. Here, we measure the evolvability of Vesicular stomatitis virus in two genetic backgrounds with different levels of mutational robustness. We passaged the viruses into a novel cell type to model a host-jump episode, quantified changes in infectivity and fitness in the new host, evaluated the cost of adaptation in the original host and analyzed the genetic basis of this adaptation. Lineages evolved from the less robust genetic background demonstrated increased adaptability, paid similar costs of adaptation to the new host and fixed approximately the same number of mutations as their more robust counterparts. Theory predicts that robustness can promote evolvability only in systems where large sets of genotypes are connected by effectively neutral mutations. We argue that this condition might not be fulfilled generally in RNA viruses.

Experimental evolution of plant RNA viruses.

Undoubtedly, viruses represent a major threat faced by human and veterinary medicines and by agronomy. The rapid evolution of viruses enables them to escape from natural immunities and from state-of-the-art antiviral treatments, with new viruses periodically emerging with deadly consequences. Viruses have also become powerful and are increasingly used tools in the field of experimental evolution. A growing body of evidence points that the evolution of viruses is mainly determined by key features such as their compacted genomes, enormous population sizes, and short generation times. In addition, RNA viruses also present large selection coefficients, antagonistic epistasis, and high mutation rates. Most of this knowledge comes from studies that have used either bacteriophages or animal viruses in cell cultures as experimental systems. However, plant viruses provide almost identical advantages for evolutionary studies and, in addition, offer an invaluable tool for studying the interplay between viruses and pluricellular hosts. Without seeking to be exhaustive, here we summarize some peculiarities of plant viruses and review recent experiments that have explored important questions on evolution, such as the role of deleterious mutation and neutrality, the effect of different transmission modes in the evolution of virulence, and the heterogeneous selective constraints imposed by multiple hosts.

Critical steps in fungal cell wall synthesis: strategies for their inhibition.

Development of new effective antifungal drugs is limited by the absence of specific target sites in the fungal cells. Knowledge of the fungal cell wall structure and biosynthesis is of interest in searching for a potential target site for new chemotherapeutic agents. Our group has demonstrated that the fungal cell wall is a metabolically active structure where interaction between distinct components occurs to give rise to the mature cell wall structure. Mannoproteins play an essential role in the cell wall organization, and there is evidence for the formation of covalent bonds between these molecules and the structural polymers (glucans and chitin) outside the plasma membrane. Such interactions, which specifically occur at the fungal cell wall, are of great interest in defining target sites for potential new chemotherapeutic agents, which may inhibit the interactions and, thus, lead to a defective cell wall formation and cell death.

Transmission bottlenecks and the evolution of fitness in rapidly evolving RNA viruses.

We explored the evolutionary importance of two factors in the adaptation of RNA viruses to their cellular hosts, size of viral inoculum used to initiate a new infection, and mode of transmission (horizontal versus vertical). Transmission bottlenecks should occur in natural populations of viruses and their profound effects on viral adaptation have been previously documented. However, the role of transmission mode has not received the same attention. Here we used a factorial experimental design to test the combined effects of inoculum (bottleneck) size and mode of transmission in evolution of vesicular stomatitis virus (VSV) in tissue culture, and compared our results to the predictions of a recent theoretical model. Our data were in accord with basic genetic principles concerning the balance between mutation, selection and genetic drift. In particular, attenuation of vertically transmitted viruses was a consequence of the random accumulation of deleterious mutations, whereas horizontally transmitted viruses experiencing similar bottlenecks did not suffer the same fitness losses because effective bottleneck size was actually determined by the number of host individuals. In addition, high levels of viral fitness in horizontally transmitted populations were explained by competition among viral variants.

Kent bundle visualized in situ at operation after unsuccessful radiofrequency ablation.

Kent bundles are seldom visualized at operation, but, in the patient described, the pathway was subepicardial, running superficial to the right coronary artery. This was probably why radiofrequency ablation failed. When this unusual pathway course is encountered, the epicardial approach should be used at operation.

Ventricular tachycardia in Duchenne's muscular dystrophy.

We report a case of a 31-year-old man with severe Duchenne's muscular dystrophy and sustained ventricular tachycardia. Serial electrophysiologic studies demonstrated the inefficiency of antiarrhythmic drugs in our patient who died after the implant of an automatic cardioverter defibrillator. A literature review is made.

Relationships between heart rate variability, functional capacity, and left ventricular function following myocardial infarction: an evaluation after one week and six months.

BACKGROUND: Relationships between heart rate (HR) variability and different prognostic markers such as ejection fraction, functional capacity, and patency of the infarct-related artery, as well as the comparison of their time courses are not fully elucidated. HYPOTHESIS: The aim of study was to assess prospectively the early postinfarction changes in HR variability and its evolution over a period of 6 months: the relationships between HR variability and functional capacity in exercise testing; left ventricular function in cardiac catheterization: status of the infarct-related artery; and the comparison of their time courses. METHODS: In 42 patients with anterior myocardial infarction, a study was made of the early changes in HR variability analyzed by the complex demodulation method, its evolution over a period of 6 months. and the relationships between HR variability and (1) functional capacity in exercise testing, (2) left ventricular function in cardiac catheterization, and (3) status of the infarct-related artery. RESULTS: At 1 week HR variability parameters correlated directly with functional capacity indicators such as METS, percent change in HR from rest to peak exercise (%deltaHR), difference between initial and peak HR (HR range), percent peak theoretical HR (% peak HR), left ventricular ejection fraction (EF), and, inversely, with end-systolic volume (ESV). Stepwise multiple regression analysis to establish HR variability parameters (recorded at 1 week) as related to functional capacity and left ventricular function at 1 week and 6 months postinfarction established the following variables: (1) At 1 week: standard deviation (SD) of the RR cycles in relation to %deltaHR (r = 0.60, p <0.0001), HR range (r = 0.43, p < 0.01), and EF (r = 0.79, p < 0.0001). (2) At 6 months, the sole accepted HR variability parameter was the SD in relation to %deltaHR (r = 0.38, p < 0.05) and HR range (r = 0.45, p < 0.01). No variability parameter was accepted in relation to METS, % peak HR, or ESV. Relationship between EF or ESV and HR variability parameters was not significant when both were evaluated at 6 months. At that time, there was a significant increase in all HR variability parameters among all surviving patients (n = 39), with the exception of the LF/HF ratio and mean RR cycle. The percent increase in HR variability between the first week and 6 months was greater among those patients with the lowest basal EF. No relation was established between HR variability and patency of the infarct-related artery. CONCLUSION: The decrease in HR variability observed following myocardial infarction is associated with a diminished functional capacity and an increased alteration of the EF. This does not affect the recovery of HR variability, which was observed in all surviving patients.

[The RICVAL study. Acute myocardial infarct in the city of Valencia. Data on 1,124 patients during the first twelve months of the registry (December, 1993--November, 1994)]. / Estudio RICVAL. El infarto agudo de miocardio en la ciudad de Valencia. Datos de 1,124 pacientes en los primeros 12 meses del Registro (diciembre de 1993-noviembre de 1994). Investigadores del RICVAL.

BACKGROUND AND OBJECTIVES: Information on the management of acute myocardial infarction in Spain is still scarce. The Register of Acute Myocardial Infarction of Valencia City (RICVAL) was established to collect, in a prospectively and uniformly way, data of patients with acute myocardial infarctions discharged from Valencia coronary care units, in order to obtain updated information on the management of these patients. Data of the first twelve months of the register are presented. METHODS: Using standardised variables, demographic, clinical, procedural and outcome data from patients with acute myocardial infarction were collected at the eight hospitals collaborating in the RICVAL, from 1 December 1993 to 30 November 1994. RESULTS: The eight participating hospitals cover 1,665,720 people. During 12 months, 1,124 patients were discharged from the participating coronary care units. Mean age was 65.1 years and 23.9% were female. The case fatality rate was 16.9%. Left ventricular failure (Killip 2, 3 and 4) was present in 42%. Thrombolytic therapy was applied in 43.5% with a median time delay of 210 minutes from chest pain onset. The delay time in initiating thrombolysis was longer in the women and in the elderly. CONCLUSION: Analysis of present data shows the feasibility of an acute myocardial infarction register in Valencia City. The RICVAL study will allow a better knowledge of demographic, clinical, procedural and outcome data in patients with myocardial infarction. The case fatality rate is still high when we consider that an acceptable level of thrombolytic therapy has been reached. The long delay time in initiating thrombolysis, particularly in the elderly and in the women, must be emphasized.

[The incidence and significance of late potentials in patients with aborted sudden death]. / Incidencia y significado de los potenciales tardíos en pacientes con muerte súbita abortada.

BACKGROUND: Reentrant ventricular tachycardia and fibrillation probably have different electrophysiological bases. Regional conduction delay during sinus rhythm seems to be greatest in patients with spontaneous sustained ventricular tachycardia than in patients with spontaneous sustained ventricular fibrillation. We investigated the prevalence and significance of late potentials in patients with documented VT or VF in the setting of coronary diseases and other organic heart diseases. PATIENTS AND METHODS: Nineteen patients with a history of spontaneous sustained ventricular tachycardia (11 patients) or fibrillation (8 patients) were studied with signal-averaged ECG. All patients had been resuscitated of sudden cardiac death. All recordings were made in sinus rhythm in an antiarrhythmic free state following the recommendations of the Committee of the European Society of Cardiology for data acquisition and analysis of ventricular late potentials using Signal Averaged Electrocardiography. The relationship between this late potentials and tachyarrhythmia inducibility during electrophysiologic study were established. RESULTS: Abnormal late potentials were found in 79% of patients with sudden cardiac death. Patients with spontaneous ventricular tachycardia had a longer ventricular activation time in sinus rhythm than did patients with spontaneous ventricular fibrillation, but this difference did not reach statistic significance. The only analysis of late potentials could not discern the mechanism of sudden cardiac death. However when sudden cardiac death was caused by a spontaneous ventricular tachycardia, a good correlation between abnormal late potentials and induced ventricular tachycardia by programmed stimulation was found. Quantitative indices of late potentials did not correlate with ventricular tachycardia cycle length. CONCLUSIONS: 1) We have found and elevated incidence of abnormal late potentials in patients with sudden cardiac death, and 2) only when the mechanism of sudden cardiac death was a spontaneous VT, we were able to correlate abnormal late potential with provoked ventricular tachycardia during electrophysiologic study.

[Survival in patients with sick sinus syndrome and artificial pacemaker. Determining clinical factors]. / Supervivencia en pacientes con enfermedad del nodo sinusal portadores de marcapasos. Factores clínicos determinantes.

INTRODUCTION AND OBJECTIVE: The hypothesis that ventricular pacing is the most important factor in the survival of patients with Sick Sinus Syndrome remains controversial. The aim of this report was to determine independent clinical variables to predict survival in paced SSS patients. METHODS: Retrospective, nonrandomized study of 153 patients with a mean age of 69 +/- 11 years, who received an initial pacemaker for Sick Sinus Syndrome between 1980 and 1994: 65 physiologic pacing (32 dual chamber, 33 atrial) and 88 ventricular pacing mode. After a maximum follow up of 177 months (median 57 months) the end point was total mortality. RESULTS: Total mortality was 21%. Using univariate analysis, single chamber ventricular pacing, age > or = 70 years and NYHA > or = 2, was associated with a higher risk for total mortality (4 times increased risk for ventricular pacing compared to other pacing modalities). Independent predictors using multivariate analysis were: 1) NYHA > or = 2 (p < 0.05). 2) Coronary artery disease (p < 0.01). 3) Chronic obstructive pulmonary disease (p < 0.05) and 4) Gender (p < 0.05). CONCLUSIONS: Mortality in patients with the Sick Sinus Syndrome is strongly predicted by preimplant baseline clinical variables. Our data indicate that the role of ventricular pacing mode remains inconclusive. A large, randomized study is necessary to confirm these results.

[Acute renal failure in critically ill patients. A prospective epidemiological study]. / Fracaso renal agudo en la unidad de cuidados intensivos. Estudio observacional prospectivo.

AIMS: To determine factors which may predict mortality in patients admitted to intensive care unit who present acute renal failure. METHODS: Prospective observational study of the patients admitted to a multidisciplinary intensive care unit over a year. The inclusion criteria were a creatinine plasmatic value > or = 2 mg/dl (177 micromol/l) or an increase (30% or higher) of its basal value on admittance. RESULTS: One hundred and twenty-seven patients (age = 65.83 +/- 15.06 years; 38% male) with acute renal failure, were prospectively enrolled in the study (13% of intensive care unit admissions). The univariate analysis showed that hospital origin, acute tubular necrosis, late ARF, oliguria, maintained hypotension, sedation or coma, oncological disease and need of mechanical ventilation were significantly associated with mortality (p < 0.05). This association was also found for sepsis (OR: 41.5), multiorganic failure (OR: 3.58) and respiratory, cardiovascular or haematological failure according to the SOFA score. The multivariate analysis found that four clinical variables had an independent predictive value for mortality risk: acute tubular necrosis [OR: 4.57 (2.32-9.00)], use of vasoactive drugs [OR: 2.32 (1.22-4.40)], oliguria [OR: 2.15 (1.12-4.13)] and the acute renal failure starting during admission [OR: 2.06 (1.09-3.88)]. CONCLUSION: Data related to renal failure have worse prognosis than other demographic or clinical data in critically ill patients with acute renal failure. Multicentric studies with unified criteria are needed to analyse the most important prognostic factors.

Amebic liver abscess with bacterial superinfection in a patient with no epidemiologic risk factors.

The amebic liver abscess is uncommon in developed countries like Spain, but the incidence is increasing probably due to the migratory movements of the population. We report a case of an amebic abscess, initially unsuspected due to the absence of epidemiologic risk factors and the negative serology for amebiasis, in the early stages of the disease.

Plasma Brain Natriuretic Peptide Levels in Cardiac Function Assessment in Chronic Dialysis Patients.

BACKGROUND: Brain natriuretic peptide (BNP) is elevated in patients with end-stage renal disease and could reflect left ventricular dysfunction. AIM: To evaluate the plasma levels of BNP in two groups of asymptomatic patients on different dialysis programs and to correlate their variations with echocardiographic parameters. METHODS: Group A consisted of 36 patients on chronic hemodialysis (HD), and group B included 38 patients on continuous ambulatory peritoneal dialysis (CAPD). ECG and echocardiography were performed, and concomitantly plasma BNP levels were determined before and after a regular 4-hour session in HD patients and before performing a dialysate exchange in patients on CAPD. RESULTS: BNP values in group A were found to be higher than in group B (419 ± 76 vs. 193 ± 56 pg/ml; p < 0.03). The cutoff point which discriminated both groups was 194 pg/ml (sensitivity: 64% and specificity: 76%; p = 0.001). Significant differences were found with respect to the following echocardiographic data (group A vs. group B): left atrial (LA) size (40 ± 13 vs. 34 ± 1 mm), LA volume (59 ± 16 vs. 41 ± 32 ml), transmitral flow E/A (1.17 ± 0.01 vs. 0.9 ± 0.06), the movement of the mitral valve annulus e/a (tissue Doppler imaging; 1.19 ± 0.15 vs. 1.05 ± 0.13) and left ventricular mass index (133 ± 10 vs. 108 ± 11). CONCLUSION: Patients on CAPD had lower levels of BNP, and echocardiographic findings indicated decreased volume overload. In asymptomatic patients, marked increases in BNP levels may reflect early stages of pathological processes that precede the development of apparent cardiac manifestations (left ventricular hypertrophy). Only echocardiographic parameters of cardiac dysfunction should be used as diagnostic criteria.