The role of the TERC-63G>A and TERT-1327C>T telomerase polymorphisms in the study of men with acute coronary syndrome.

AIM: Telomerase is a ribonucleoprotein that maintains telomere length. Telomeres and telomerase are involved in cellular ageing and have been connected to some ageing related diseases, like cardiovascular disease. Telomerase dysfunction could be the main underlying mechanism in this connection but this point is still unclear. The aim of this article is to investigate the possible influence of cellular ageing, measured by two telomerase polymorphisms, TERC-63G>A (rs2293607) and TERT-1327C>T (rs2735940), on the whole spectrum of acute coronary artery disease (CAD). METHODS: We studied 150 middle aged men admitted for an acute coronary syndrome (ACS). Cardiovascular risk factors prevalence was collected at admission. Severity variables analyzed were Killip class and number of vessels affected. Telomerase polymorphisms were studied by real time PCR in DNA samples extracted from peripheral blood leukocytes. Clinical follow-up had been developed for more than 600 days and a prognostic combined event was defined. RESULTS: C allele of TERT polymorphism was more prevalent among hypertensive patients (OR: 3.19; 95% CI: 1.37-7.42; P=0.006). None of polymorphisms showed any prognostic value or relation to CAD severity. CONCLUSION: Telomerase dysfunction could be involved in hypertension prevalence. This finding could support new screening strategies in high risk population. The two telomerase polymorphisms analyzed did not show any prognostic value or connection to CAD severity. However, further studies are required to determine the molecular mechanisms responsible for cellular ageing in ACS.

[Thrombolysis in the elderly with acute myocardial infarction. The PRIAMHO study]. / Trombólisis en el anciano con infarto agudo de miocardio. El estudio PRIAMHO.

INTRODUCTION: In the elderly with acute myocardial infarction the risks and benefits of thrombolytic therapy are not well defined due mainly to the lack of randomized trials. In the present study we examined the clinical profile of the aged treated with thrombolytic agents and the effects of that therapy on 28 day and 1 year mortality. PATIENTS AND METHODS: We studied 733 patients aged > 75 years (mean: 79.9) admitted to the Coronary Care Unit (CCU) of 24 Spanish hospitals with a confirmed diagnosis of Q-Wave myocardial infarction (MI). On admission, 293 patients were treated with thrombolytics and 440 patients received standard therapy. The difference between the two groups in the clinical profile of MI, treatments administered in CCU, evolutive course and 28 day and 1 year mortality were assessed. RESULTS: The independent predictors related to the use of thrombolytic therapy were age (OR: 0.93; 95% CI: 0.89-0.97), history of arterial hypertension (OR: 0.85; 95% CI: 0.71-1.01), delay time to admission (OR: 0.998; 95% CI: 0.997-0.999), anterior location of infarct (OR: 1.21; 95% CI: 1.01-1.24) and Killip Class III-IV (OR: 0.79; 95% CI: 0.64-0.97). During the evolution thrombolysis therapy was associated with lower rates of Killip III-IV (p < 0.00001), complete AV block (p = 0.037), intraventricular conduction defects (p = 0.046) and a higher incidence of stroke (p < 0.01). The 28-day mortality was also significantly lower in the group receiving thrombolytics (27 vs 31. 3%; p = 0.035). However, this difference disappeared when the analysis was adjusted with other variables such as age, administration of aspirin and Killip Class III-IV (OR: 1.29; 95% IC: 0.87-1.92). CONCLUSIONS: The results of this trial suggest that in the elderly with acute myocardial infarction thrombolysis is associated with a less complicated evolutive course and a lower 28-day mortality. However, these findings could be mediated by other covariables such as age, more frequent use of aspirin and a higher number of patients with Killip Class III-IV excluded from the thrombolytic therapy.

Tratamiento de la angina de pecho / Treatment of angor pectoris

La angina de pecho es la forma más común de manifestarse la cardiopatía isquémica. El paciente que presenta dolor anginoso es afortunado porque dentro del amplio abanico de manifestaciones de la cardiopatía isquémica, cualquiera de las otras como infarto de miocardio, muerte súbita, insuficiencia cardíaca y arritmias ventriculares, son más graves y porque, además, la presencia del dolor torácico permite poner en marcha todo el sistema diagnósticoterapéutico que redundará finalmente en una reducción del infarto de miocardio y la muerte. El tratamiento de la angina de pecho, tanto en su forma crónica y estable como en la forma aguda e inestable, tiene como objetivos inmediatos controlar el síntoma y prevenir la muerte y el infarto agudo, y como objetivos a medio y largo plazo el control de la enfermedad aterosclerótica coronaria. El plan terapéutico siempre deberá diseñarse según el perfil de riesgo de cada paciente.La angina inestable frecuentemente se estabiliza con tratamiento médico, pero puede presentar inicialmente predictores de mal pronóstico o en la fase pre-alta hospitalaria una prueba de isquemia moderada o severamente positiva, que determinarán una actitud agresiva con angiografía coronaria y eventualmente revascularización. En la angina crónica, el tratamiento médico, que se dirige a controlar síntomas pero también a prevenir infarto y muerte, debe también configurarse atendiendo a tres variables de significación pronóstica, grado de isquemia, estado de la función ventricular y extensión angiográfica de la enfermedad coronaria. Según el perfil pronóstico de cada paciente se decidirá el tipo de tratamiento definitivo. Los casos con mayor riesgo se beneficiarán de un tratamiento revascularizador y la técnica a proponer se establecerá en función de la localización y extensión de las lesiones anatómicas, la severidad de la i quemia y el grado de disfunción ventricular. (AU)

[Unstable angina in the elderly: clinical, profile, management and mortality at three months. The PEPA Registry Data]. / Angina inestable en el anciano: perfil clínico, manejo y mortalidad a los tres meses. Datos del registro PEPA.

INTRODUCTION AND OBJECTIVES: Few reports in the literature have studied the characteristics and management of unstable angina in the elderly in Spain. The aim of this study was to analyze the clinical characteristics and the use of diagnostic and therapeutic resources in patients > or = 70 years of age. PATIENTS AND METHODS: A total of 1,551 patients > or = 70 years of age were included out of 4,115 included in the PEPA registry with a follow up of 90 days. These patients were compared with 2,564 < 70 years. RESULTS: In comparison, the elderly (76 +/- 5 years) versus the younger group (58 +/- 8.5 years) included a higher proportion of women (43 vs 27%), diabetics (30 vs 23%)and hypertensive patients (60 vs 49%) with a lower proportion (p < 0.001) of hypercholesterolemia (33 vs 43%), smoking (40 vs 60%) or family history (9 vs 17%). A previous history of angina (49 vs 35%) or infarction (38 vs31%) and comorbidity was found to be significantly more frequent in the elderly, with a worse previous functional class (NYHA > 2 out of 34 vs 15%). The elderly were treated with fewer invasive procedures (25 vs 44%) or catheterization (26 vs 36%) and they were more frequently controlled with medical treatment (86 vs 83%) although with a lower use of beta blockers (45 vs 53%). The mortality at 3 months was greater in the elderly (7.4 vs 3.0%;p < 0.005) with age being an independent predictor of bad prognosis. Cox multivariate analysis showed the age, ST segment depression, diabetes and heart failure on admission to be predictors of bad prognosis in the elderly. CONCLUSIONS: A different pattern is observed in cardiovascular risk factors with a more unfavorable clinical profile in elderly patients with unstable angina. The management of these patients is less aggressive and the mortality is greater. Diabetes, heart failure and ST segment depression on admission are independent predictors of bad prognosis in elderly patients.

[The effect of the mean platelet volume on the short-term prognosis of acute myocardial infarct]. / Influencia del volumen plaquetario medio sobre el pronóstico a corto plazo del infarto agudo de miocardio.

INTRODUCTION AND OBJECTIVES: The increase of mean platelet volume in the late phase of myocardial infarction is an independent predictor for recurrent myocardial infarction and death, but the association between this finding and the short-term prognosis after acute myocardial infarction is unknown. The goals of this study were to assess the influence of mean platelet volume on the risk of death, recurrent ischemic events or cardiac heart failure during the in-hospital phase of myocardial infarction and to analyse the relationship between mean platelet volume and several demographic and clinical variables registered on admission. MATERIAL AND METHODS: A population of 1,082 patients with acute myocardial infarction were distributed in two groups according to the platelet volume measured on admission: group 1, mean platelet volume > 9 fl (n = 443) and group 2, mean platelet volume < or = 9 fl (n = 639). The difference between both groups on the end-point of this study were assessed by univariate and multivariate statistical methods. An univariate analysis was also applied to assess the relationship between platelet volume and the baseline variables. RESULTS: A mean platelet volume > 9 fl was associated with a significant increase of risk for the combined end-point considered (OR = 1.37; p = 0.026). By univariate analysis, an increased platelet volume was related to a higher risk of cardiac failure (OR = 1.46; p = 0.01) and a non-significant increase in the incidence of recurrent ischemic events (OR = 1.35; p = 0.07). In addition, a large platelet volume was also associated with a higher prevalence of prior myocardial infarction, arterial hypertension and diabetes mellitus. CONCLUSIONS: The results of this study suggest that the increase of mean platelet volume on admission is an independent risk factor for cardiac heart failure and is associated with a non significant higher rates of ischemic events during the recovery phase of acute myocardial infarction.

[Appraisal of the state of the autonomic nervous system in hypertrophic cardiomyopathy by the analysis of heart rate variability]. / Aproximación al conocimiento del estado del sistema nervioso autónomo en la miocardiopatía hipertrófica mediante el análisis de la variabilidad de la frecuencia cardíaca.

INTRODUCTION: The analysis of heart rate variability has been accepted as a non-invasive method to evaluate the influence of the autonomic nervous system over the heart. Although heart rate variability has been used during the last decade in several illnesses the studies in hypertrophic cardiomyopathy are scarce. OBJECTIVES: We report the activity of the autonomic nervous system in patients with hypertrophic cardiomyopathy using the analysis of heart rate variability. PATIENTS AND METHODS: Heart rate variability was evaluate by the analyzing 24-h ambulatory electrocardiograms (Holter) in 20 patients with hypertrophic cardiomyopathy and in 15 controls. This method has been used to measure heart rate variability. Spectral analysis of the frequencies were calculated using fast Fourier transformation. Spectral heart rate variability was computed as high (0.15 to 0.40 Hz) low (0.04 to 0.15 Hz) and total (0.01 to 1.0 Hz). We compared the relation between low/high frequency as an index of the sympathetic/parasympathetic balance. All data are expressed as mean value +/- SD. The unpaired Student t-test was used. A two tailed p valued < 0.05 was considered statistically significant. RESULTS: There were no differences in the mean heart rates among the patients with hypertrophic cardiomyopathy and normal subjects (mean +/- SD: 71 +/- 9 versus 74 +/- 11 beats/minute; p = NS) while there was a significant decline in total spectral (mean +/- SD: 7.14 +/- 1.1 versus 7.57 +/- 0.6 ln [ms2]; p = 0.02) and high (mean +/- SD: 5.22 +/- 0.8 versus 5.63 +/- 1.3 ln [ms2]; p = 0.04) as well as in low spectral frequency of heart rate variability (mean +/- SD: 22 +/- 0.8 versus 5.63 +/- 1.3 ln [ms2]; p = 0.04) in patients with hypertrophic cardiomyopathy. There were no differences in the low/high frequency component ratio in these patients (mean +/- SD: 1.1 +/- 0.1 versus 1.2 +/- 0.1 ln [ms2]; p = NS). CONCLUSIONS: These facts suggest that the patients with hypertrophic cardiomyopathy have an alteration in the autonomic nervous system: sympathetic (low spectral frequencies) and parasympathetic activity (high spectral frequencies), although this does not reflect an imbalance between sympathetic and parasympathetic activities (relation of low to high spectral frequencies).

[Clinical characteristics and hospital mortality of acute myocardial infarction in elderly patients treated with thrombolytic agents]. / Características clínicas y mortalidad hospitalaria del infarto agudo de miocardio en ancianos tratados con fármacos trombolíticos.

OBJECTIVES: This study describes the clinical features of elderly patients with acute myocardial infarction treated with thrombolytics and the effect of such therapy on in-hospital mortality rates in these patients. METHODS AND RESULTS: A group of 463 consecutive patients older than 70 years with an acute myocardial infarction was studied. This population was divided into two groups: 157 patients who received thrombolytic therapy (group A) and 306 patients who did not (group B). Patients in group A were younger (77 vs 79 years; p = 0.01) and had a lower prevalence of females (32.5% vs 44.1%; p = 0.01), prior myocardial infarction (14% vs 28%; p = 0.0008), hypertension (38% vs 48%; p = 0.03), diabetes (17% vs 26%; p = 0.02), class Killip 3 at entry (3.5% vs 14%; p = 0.001), a higher frequency of Q wave MI (88% vs 50%; p = 0.0001), inferior location of MI (51% vs 32%; p = 0.00007) and Killip 1 (70% vs 57%; p = 0.01) compared to group B. No significant differences on the inhospital mortality between either group were observed (25.5% vs 24.8%; p = 0.88). However, the thrombolysis was associated with higher mortality in patients with left ventricular dysfunction at entry (41% vs 84%; p = 0.0008) and in those patients with a delay of more than four hours from the onset of symptoms to admission (19% versus 30%; p < 0.1). CONCLUSIONS: 1) In the elderly with acute myocardial infarction, thrombolytic therapy is administered to a lower risk population; 2) our findings do not confirm the benefits of chemical thrombolysis on cardiac mortality in the elderly, and 3) in selected subgroups (Killip > 2 at entry, symptoms delay > 4 hours) the risk/benefit ratio of thrombolytic therapy should be reevaluated. However, care needs to be taken in evaluating the data because this study was not blinded and the number of patients included was relatively small.

[Cardiomyopathy (X). Clinical approach to the patient with hypertrophic cardiomyopathy]. / Miocardiopatías (X). Actitud clínica ante el paciente con miocardiopatía hipertrófica.

Hypertrophic cardiomyopathy is a clinical and anatomofunctional entity that determines a series of hemodynamic consequences closely related to sintomatology. Left ventricular hypertrophic, subaortic stenosis, diastolic dysfunction and myocardial ischemia are the different pathophysiology mechanisms that generate similar clinical manifestations. Sintomatology defines two groups of patients with different profiles and clinical management. Ventricular arrhythmias are not uncommon and the forms that imply a darkest prognosis are supported symptomatic ventricular tachycardia and the induced ventricular tachycardia in patients that have suffered a cardiac arrest or have had syncopes. Basic explorations in all patients, in addition to physical examination, chest radiography and rest electrocardiogram, are Doppler echocardiography and Holter. Other explorations, such as Tallium-201 stress test, tilt test, electrophysiological and hemodynamic studies, are rationalized according to risk profile, sintomatology and responses to indicated treatment. In general, prognosis in asymptomatic patients is good and complex explorations are not justified nor are preventive character treatments. Symptomatic patients who have a higher risk must be studied more closely, and frequently require complex and invasive explorations. They also need pharmacological treatment and often more invasive therapeutical options, DDD pacemakers or surgery, if those fail.

[Study of heart rate variability in acute myocardial infarction and its relationship with ventricular function and other clinical variables]. / Estudio de la variabilidad de la frecuencia cardíaca en el infarto agudo de miocardio y su relación con la función ventricular y otras variables clínicas.

BACKGROUND: The influence of ventricular function (VF) on prognosis in acute myocardial infarction (AMI) is well known. Heart rate variability (HRV), as a neurohumoral parameter could predict VF after discharge in AMI patients. Our goal is to investigate the possible relation among HRV, VF and another clinical variables in AMI. PATIENTS AND METHODS: We studied 37 patients with AMI after hospital discharge. Age, AMI type, location, enzymes, treatment (thrombolysis versus no thrombolysis) were evaluated. The left ventricular ejection fraction (LVEF) was assessed by radionuclide ventriculography in 27 subjects. Twenty nine subjects without cardiopathy were the control group. Twenty four hour electrocardiographic recordings were obtained and a proper software was used to measure HRV. This was evaluated with time domain measures: RR interval, standard deviation of the mean RR interval (SDNN), standard deviation of the average of the RR intervals measured every 5 minutes during 24 hours (SDANN) and number of two consecutive RR intervals with a variability > 50 ms (pNN50). We considered a decreased variability if SDANN was less than 100 ms. Two groups were established: 1) low heart rate variability (LHRV) if SDANN was less than 100 ms, and 2) normal heart rate variability (NHRV) if SDANN was larger than 100 ms. Continuous variables were examined by the t-test, chi square for discrete ones and linear regression analysis was used to assess the relation among variables. A p < 0.05 was considered significant. RESULTS: The percentage of infarcted patients in the group of LHRV is 75%, whereas it is 14% in the control group (p < 0.05). SDANN, SDNN and pNN50 values are significantly lower (p < 0.05) in the AMI than in the control group. LHRV was more frequent in patients with complicated AMI with congestive heart failure. LVEF was significantly lower (35% vs 56%) in the LHRV than in the NHRV group. No significant differences were found among: site, type infarct, treatment or ventricular ectopy in the Holter before discharge. There is good correlation (r = 0.635; p < 0.05) between LVEF and HRV measures. No correlation was found between HRV and age, or the enzymatic size of infarction. CONCLUSIONS: 1) LHRV is frequent in the late phase of AMI, and 2) LHRV can be an indirect index of left ventricular failure.

Isosorbide dinitrate sublingual therapy for inferior myocardial infarction: randomized trial to assess infarct size limitation.

To assess the potential of isosorbide dinitrate sublingual therapy for limiting myocardial infarct size, 41 patients with inferior acute myocardial infarction (AMI) were studied. Twenty patients were randomly assigned to the control group and 21 to the treatment group. Patients in the treatment group received 10 mg of isosorbide dinitrate every 2 hours for 72 hours. To estimate infarct size, QRS scoring, peak creatine kinase (CK) serum levels and CK curves were used. There were no significant differences between the 2 groups in maximal or cumulative activity of CK or QRS score (percent of left ventricle infarcted: 16% in the control group, 17% in the treatment group). In both groups the QRS score increased significantly by 13 hours after AMI, and the increase was highly significant by 19 to 23 hours. Thus, sublingual isosorbide dinitrate at the dosage given did not reduce infarct size in patients with inferior AMI.

[Permanent endocardial pacemaker. Review of 116 implantations (author's transl)]. / Marcapaso endocavitario permanente. A propósito de 116 implantaciones.

A retrospective study on the results of 116 permanent ventricular pacemaker implantations performed in the Service of Cardiology of the Hospital Clinico Universitario in Salamanca is reported. In the majority of cases the indication for a pacemaker was a complete atrioventricular block (53 cases). Sixteen cases had a "sick-sinus syndrome". An apparent cardiopathy was not found in 84 percent of the cases. In the group of patients with cardiopathy that of ischemic type was the most common. The technique of endocardiac catheter pacing was employed in all cases. An 18 percent of global complications occurred, but in no case an early electrode displacement was registered. Complications appeared at a later time included erosion of the pacemaker in ten cases, and displacement and/or deinsertion in seven. The mean life for 18 displaced generators was 41.3 months. A sudden equipment malfunction occurred in two cases, and an inhibition by potentials of the pectoralis major muscle in another. Morbidity rate was lower to that of other published series, may be due to the use of modern generators with a progressive reduction of its diameter and weight and more flexible electrodes which allow a better implantation. The mortality rate was zero.