Diferencias de género en la titulación de fármacos de pacientes con insuficiencia cardiaca y fracción de eyección reducida del ensayo ETIFIC / Gender differences in drug titration among heart failure patients with reduced ejection fraction in the ETIFIC trial

Introducción y objetivos El tratamiento óptimo disminuye la mortalidad y hospitalizaciones por insuficiencia cardiaca (IC) en pacientes con IC y fracción de eyección reducida. En los ensayos clínicos las mujeres estuvieron infrarrepresentadas y no fueron evaluadas específicamente. Este estudio buscó comparar la seguridad y efectividad de titulación (ajuste de dosis) de fármacos en mujeres y varones. Métodos Estudio post hoc de género del ensayo aleatorizado multicéntrico ETIFIC. Se incluyeron pacientes hospitalizados con IC de novo y fracción de eyección reducida. Proceso estructurado de titulación en unidades de IC. Objetivo principal: la dosis relativa media de bloqueadores beta (% de la dosis objetivo) alcanzada por mujeres frente a varones. Objetivos secundarios: dosis relativas medias de otros fármacos de IC, eventos adversos y resultados clínicos a 6 meses. Resultados Se incluyeron 320 pacientes, 83 (25,93%) mujeres y 237 (74,06%) varones. (76 frente a 213 analizados). Media±desviación estándar de dosis relativa de bloqueadores beta mujeres frente a varones: 62,08±30,72% frente a 64,4±32,77%; diferencia −2,32%; IC95%, −10,58-5,94; p=0,580, antagonistas del receptor de mineralocorticoides 79,85±27,72% comparado con 67,29±31,43%; p=0,003, sin diferencias significativas en dosificación de otros fármacos. El análisis multivariante no encontró diferencias significativas. Mortalidad cardiovascular 1 (1,20%) frente a 3 (1,26%), p=1 y 0 hospitalizaciones por IC (0,00%) frente a 10 (4,22%), p=0,125. Conclusiones En un análisis post hoc del ensayo ETIFIC de titulación en IC no encontramos diferencias de género significativas en dosificación, mortalidad cardiovascular y hospitalizaciones por IC (AU)

Introduction and objectives Optimal medical therapy decreases mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. Women have been underrepresented in clinical trials and not specifically evaluated. This study aimed to compare the safety and effectiveness of drug titration in women vs men. Methods This post hoc gender study of the ETIFIC multicenter randomized trial included hospitalized patients with new-onset HF with reduced ejection fraction and New York Heart Association II-III and no contraindications to beta-blockers. A structured 4-month titration process was implemented in HF clinics. The primary endpoint was the mean relative dose (% of target dose) of beta-blockers achieved by women vs men. Secondary endpoints included the mean relative doses of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists, adverse events, and other clinical outcomes at 6 months. Results A total of 320 patients were included, 83 (25.93%) women and 237 (74.06%) men (76 vs 213 analyzed). The mean±standard deviation of the relative doses achieved by women vs men were as follows: beta-blockers 62.08%±30.72% vs 64.4%±32.77%, with a difference of−2.32% (95%CI,−10.58-5.94), P = .580; and mineralocorticoid receptor antagonists 79.85%±27.72% vs 67.29%±31.43%, P =.003. No other differences in drug dosage were found. Multivariate analysis showed nonsignificant differences. CV mortality was 1 (1.20%) vs 3 (1.26%), P=1, and HF hospitalizations 0 (0.00%) vs 10 (4.22%), P=.125. Conclusions In a post hoc analysis from the HF-titration ETIFIC trial, we found nonsignificant gender differences in drug dosage, cardiovascular mortality, and HF hospitalizations (AU)

Clustering of target organ damage increases mortality after acute coronary syndromes in patients with arterial hypertension.

The impact of target organ damage (TOD) clustering in hypertensive patients with established cardiovascular disease has not been clearly defined. Multicentre, observational and prospective study of 1054 consecutive patients with acute coronary syndromes (ACSs). The objective was describing the impact of TOD on first-year mortality. Ankle-brachial index (ABI), left ventricular hypertrophy and renal dysfunction were assessed during hospital stay. Hypertensive patients accounted for 80% of the cohort and had slightly higher mean age, higher prevalence of risk factors, previous cardiovascular disease and TOD. During follow-up, mean time 387.9 (7.2) days and median 382 (364.0-430.0) days, mortality rate tended to be higher in hypertensive patients (6.1 versus 3.5%; P=0.16). Cox regression survival analysis identified pathological ABI as the only TOD independently associated with mortality. When assessed globally, the presence of at least one TOD predicted mortality only in patients with hypertension and differences in mortality rate appeared very early in the follow-up. A linear increase in mortality rate was observed with the clustering of TOD: 2.0%, if no TOD was present, 7.6% in one TOD, 11.1% in two TODs and 20.0%, if three TODs were present. An increased risk in the combined end point of ischaemic events was observed in hypertensive patients without TOD (odds ratio (OR): 3.18; 95% confidence interval (CI): 1.31-7.70; P=0.01) and was still higher in patients with hypertension and TOD (OR: 4.61; 95% CI: 1.90-11.80; P<0.01). TOD predicts mortality and ischaemic events of hypertensive patients after ACS.

Prevalence and prognostic influence of peripheral arterial disease in patients >or=40 years old admitted into hospital following an acute coronary event.

OBJECTIVE: A significant proportion of patients with ischemic heart disease have associated peripheral arterial disease (PAD), but many are asymptomatic and this condition remains underdiagnosed. We aimed to study the prevalence of PAD in patients with an acute coronary syndrome (ACS) and to evaluate its influence in hospital clinical outcomes. METHODS: The PAMISCA register is a prospective, multicenter study involving patients >or=40 years old with ACS admitted to selected Spanish hospitals. All patients had their ankle-brachial index (ABI) measured between days 3 and 7 after the ischemic event. RESULTS: 1410 ACS patients (71.4% male) were included. PAD determined by ABI was documented in 561 patients (39.8%). Factors independently related to PAD were age (OR: 1.04; 95% CI: 1.03-1.06; p<0.001), smoking (OR: 1.88; 95% CI: 1.41-2.49; p<0.0001), diabetes (OR: 1.30; 95% CI: 1.02-1.65; p<0.05), previous cardiac disease (OR: 1.54; 95% CI: 1.22-1.95; p<0.001) and previous cerebrovascular disease (OR: 1.90; 95% CI: 1.28-2.80; p<0.001). Following the ACS, an ABIor=40 years presenting with ACS is high and it is associated with increased cardiovascular risk.

Long-term results of the Spanish trial on treatment and survival of patients with predominantly mild heart failure.

A randomized open-label clinical trial was conducted to determine whether mortality, readmission, or quality of life differed between heart failure patients managed with captopril plus diuretics and those with digoxin plus diuretics. A total of 345 heart failure patients in New York Heart Association functional classes 2 and 3 without atrial fibrillation, dyspnea of bronchopulmonary origin, or hypertension not controlled with diuretics was randomized for digoxin (n = 175) or captopril (n = 170) treatment and followed up for a median of 4.5 years. Socioeconomic, demographic, electrocardiographic, echocardiographic, spirometric, and chest radiograph data were obtained at the initial examination. In a random sample of half the patients, ergometric, echocardiographic, and Holter records were obtained at entry and at 3 and 18 months. Patients were followed up for > or = 3 years. The end points were mortality, hospitalization for cardiac events, deterioration in quality of life, worsening of functional class, and need for digoxin or captopril in the captopril and digoxin groups, respectively. The trial had to be terminated prematurely owing to the difficulty in finding candidates free of angiotensin-converting enzyme (ACE)-inhibitor treatment. Baseline patient characteristics were similar in both groups. From the clinical point of view, only the 48-month mortality was relevantly lower (20.9 vs. 31.9%, respectively) among patients treated with captopril than that in those receiving digoxin (log rank test, p = 0.07). No statistically or clinically relevant differences were found in other end points or adverse effects. The results suggest but do not confirm the hypothesis that captopril treatment in mild to moderate heart failure might provide better long-term survival than digoxin.

[Atherosclerotic coronary ectasia or a lymphomucocutaneous syndrome in an adult (Kawasaki's disease)?]. / Ectasia coronaria aterosclerótica o síndrome linfomucocutáneo del adulto (enfermedad de Kawasaki)?

We report the case of a 42-year-old man, who was admitted to hospital with an inferior myocardial infarction. He was treated with tissue plasminogen activator without complications in the acute phase. The stress testing performed before discharge showed residual myocardial ischemia. A catheterization study was indicated. The coronary angiogram demonstrated diffuse three vessel coronary artery aneurysmal disease. Two years before the patient had an aneurysm of the right iliac artery being operated on. The differential diagnosis of adult aneurysmal coronary disease is discussed with emphasis on Kawasaki's disease and atherosclerotic coronary artery ectasia.

[Thrombus in the thoracic aorta as cause of peripheral embolism diagnosed using transesophageal echocardiography]. / Trombo en aorta torácica como causa de embolismo periférico diagnosticado por ecocardiografía transesofágica.

The authors report the cases of two patients, with no risk factors for thromboembolism, in whom a mobile thrombus of the thoracic aorta was diagnosed by transesophageal echocardiography, after an episode of systemic embolism. The outcomes of the two cases were very different. In one patient the thrombus was no longer present after anticoagulant treatment with no recurrent embolic event. The other patient had a new embolic event and the thrombus persisted while having anticoagulant therapy. This patient underwent surgery, and the thrombus was removed. These cases illustrate the value of transesophageal echocardiography in the detection of embolic source.

[Carcinoma of the Bellini's collecting duct: report of 2 new cases]. / Carcinoma del conducto colector de Bellini: aportación de dos nuevos casos.

Report on two new cases of Bellini's collector duct carcinoma (CTC), discussing the clinical, radiological and pathological aspects which differentiate this disorder from the clear cells carcinoma, and review of the related literature.

[The effect of antihypertensive therapy on left ventricular mass and diastolic filling in light and moderate hypertension]. / Efecto de la terapia antihipertensiva sobre la masa ventricular izquierda y el llenado diastólico en la hipertensión ligera a moderada.

BACKGROUND: To valorate the effect of four antihypertensive drugs on the regression of cardiac mass and diastolic function, by echocardiography-Doppler, in not treated hypertensive subjects. METHODS: 60 mild-moderate hypertensive subjects were studied randomized in four groups of 15 patients each one: enalapril (10-40 mg/d), atenolol (25-100 mg/d), verapamil-retard (120-240 mg/d), alphametildopa (250 mg/8h to 3 g/d). The active drug therapy phase was 6 months, performing echo-Doppler, evaluating posterior-wall and septal-wall thicknesses, ventricular mass index, ratio of early to atrial peak diastolic filling velocity (E/A), the first-third filling fraction and atrial filling fraction. RESULTS: The cardiac mass index decreased with the four drugs: with enalapril from 178 +/- 28 to 155 +/- 29 g/m2 (p < 0.05), with atenolol from 170 +/- 23 to 154 +/- 19 g/m2 (p < 0.05), with verapamil from 180 +/- 27 to 159 +/- 22 g/m2 (p < 0.05) and with alphametildopa from 176 +/- 30 to 142 +/- 22 g/m2 (p < 0.01). The E/A ratio and first-third filling fraction only improved in the atenolol subgroup, from 0.79 +/- 0.13 to 0.97 +/- 0.16 (p < 0.01) and from 36 +/- 5 to 44 +/- 9% (p < 0.01), decreasing atrial filling fraction from 37 +/- 6 to 30 +/- 8% (p < 0.01), without modifying with enalapril (0.74 +/- 0.14 to 0.76 +/- 0.20, 35 +/- 5% to 36 +/- 7%, 38 +/- 5 to 39 +/- 7%, p = NS), verapamil (0.69 +/- 0.12 to 0.74 +/- 0.17, 35 +/- 6% to 36 +/- 8% to 40 +/- 12%, p = NS) neither alphametildopa (0.72 +/- 0.14 to 0.71 +/- 0.21, 34 +/- 5% to 35 +/- 7%, 40 +/- 6% to 41 +/- 9%, p = NS). The heart rate decreased more with atenolol than with the other drugs (61 +/- 15 vs 71 +/- 12, p < 0.01). CONCLUSIONS: In hypertensive patients the decreasing of cardiac mass is not accompanied of improvement of the diastolic function except in patients treated with atenolol, probably due to bradycardia.

[The 2-dimensional and Doppler color echocardiographic study of a congenital aneurysm of the sinus of Valsalva with a fistula of the right atrium in an adult]. / Estudio con ecografía bidimensional y Doppler en color de un aneurisma congénito del seno de Valsalva con fístula a la aurícula derecha en un adulto.

This report describe a 69-year old woman with a congenital aneurysm of the non-coronary sinus of Valsalva ruptured in the right atrium, causing severe hemodynamic derangement of the right ventricle. The site of the communication between the aneurysm and the receiving chamber was accurately diagnosed by two-dimensional color flow Doppler imaging which provided more valuable preoperative information than conventional aortography.

[Doppler analysis of mitral flow in mild to moderate hypertension]. / Análisis de la curva de flujo Doppler mitral en la hipertensión arterial leve a moderada.

We evaluate by Echo-Doppler the left ventricular relaxation disturbance produced by mild to moderate hypertension. It's a comparative study between 15 healthy and 40 patients with hypertension (diastolic blood pressure between 90-114 mmHg and/or systolic greater than 160 mmHg). Echocardiography was performed in all cases and diameters, thickness, volumes, ejection fraction, mass, transmitral flow by Doppler and cardiac output were evaluated . In hypertensive patients the septal and posterior wall thicknesses were significantly higher (1.39 +/- 0.2 cm vs 1.1 +/- 0.1, p less than 0.001 cm. and 1.26 +/- 0.12 cm vs 0.98 +/- 0.1 cm, p less than 0.001), and also the absolute mass and corrected according to corporal surface (339 +/- 58 g vs 203 +/- 44, p less than 0.001, and 185 +/- 34 g/m2 vs 115 +/- 16, p less than 0.001). In transmitral flow Doppler the higher isovolumetric period and lower diastolic filling in the first 1/3 (71 +/- 19 msec vs 53 +/- 20, p less than 0.05, and 35 +/- 5% vs 52 +/- 4%, p less than 0.001) are indicators of relaxation disturbance. A lower deceleration of early inflow and a higher deceleration time (265 +/- 98 cm/sec2/vs 454 +/- 139, p less than 0.001, and 226 +/- 38 msec vs 156 +/- 15, p less than 0.001) show compliance damage. The atrial filling was significantly higher in hypertensive patients (37 +/- 7% vs 20 +/- 8%, p less than 0.001). The E/A ratio, separate both groups but corrected by the age the signification was rather lower.(ABSTRACT TRUNCATED AT 250 WORDS)

In situ right gastroepiploic artery. A conduit for coronary revascularization.

The internal mammary artery is widely recognized as the graft of choice for coronary artery bypass grafting at present. Alternative conduits have been investigated in order to find other adequate long-term grafts. The right gastroepiploic artery has been recently used as a graft to bypass distal coronary vessels. From November 1989 to June 1990, we have implanted this artery in 46 cases. Pedicled grafts were implanted in 20 patients to the main right coronary artery, in 21 patients we grafted the right distal branches, in 3 patients the left anterior descending, and in 2 the circumflex branches. Mean grafts per patient were 3 in this series, with a mean of 2.2 arterial grafts per patient. One patient died in the early postoperative period. The remaining patients had an uncomplicated postoperative evolution. Thirteen patients underwent graft and coronary angiography. Direct or indirect graft patency was confirmed in all cases. The final important issue concerning the long-term patency of this graft will be solved in the future, but short-term patency rates of the right gastroepiploic artery can be anticipated when proper techniques are used.

[Urethral diverticulum in the male]. / Divertículos de uretra en el varón.

We report on a 50-year-old male patient with acquired urethral diverticulum complicated by calculus in the anterior urethra. The etiologic factors, the hypotheses put forward relative to the pathogenesis of urethral diverticulum, its diagnosis and forms of treatment are discussed.

[Double outlet right ventricle with situs inversus. Surgical treatment of a case with interventricular communication and pulmonary stenosis]. / Doble salida del ventrículo derecho con situs inverso. Tratamiento quirúrgico de un caso con comunicación interventricular y estenosis pulmonar.

A 4-year-old patient with situs inversus, double outlet right ventricle, septal defect, and pulmonary stenosis has been surgically corrected. During operation a tubular patch was used to communicate left ventricle with the aorta. Cross-sectional echocardiography was performed in order to test correct position of the graft.

[Prostaglandins in newborn infants with severe cardiopathy]. / Las prostaglandinas en el neonato con cardiopatía grave.

Between February 1983 and December 1985 authors have studied 26 newborn infants with severe congenital heart disease who received prostaglandin E1 infusion as therapy. Onset of therapy was before 5 days of age in 15 patients, between 5 and 7 days of age in 7 cases and after 14 days of age in the remaining ones. Initial dose was 0.05 mcg/kg/minutes and mean duration of infusion was 131.9 +/- 19.0 hours. Patients were divided into 3 groups according to pulmonary and systemic blood flows: Group I, with cyanosis and diminished pulmonary blood flow (12 cases); Group II, with diminished systemic blood flow (10 cases); and group III, with cyanosis and normal or increased pulmonary blood flow (4 cases). Most patients of groups I (10/12) and II (9/10) improved levels of blood PO2: mean increments of 17.8 +/- 7.4 and 17.5 +/- 13.3 torr respectively. Peripheral pulses also improved in four extremities in patients from group II; systolic and diastolic pressures increased 16 +/- 9.6 and 5 +/- 2.2 mmHg, respectively. No improvement was observed in patients from group III, with exception of patients with transposition of great vessels. Most frequent complication of prostaglandin infusion was hyperthermia, which was observed in 16 cases but disappeared in all with moderate reduction of doses. Appropriate surgery was performed in 19 patients, with an overall survival of 52.6%. In conclusion, prostaglandin infusion appears to be a very valued tool to improve the hemodynamic condition in newborn infants with severe congenital heart disease and thus allow the practice of corrective surgery during first month of life.

[Mitral atresia. Anatomical study and surgical implications]. / Atresia mitral. Estudio anatómico e implicaciones quirúrgicas.

We present the pathological study of 17 cases of mitral atresia with patent aortic valve and their surgical implications. The study is based on the type of atrioventricular connection, presence or absence of ventricular septum, size of the left ventricle and relation of the aorta with the aforementioned ventricle. We have classified mitral atresia into two groups by assessing these data. Group A) Both ventricles and atrioventricular connections are present and there is ventricular septal defect. The aorta may connect with an either normal or hypoplastic left ventricle or it may emerge in double outlet from the right ventricle. Group B) Absent left ventricle and atrioventricular connection. The aorta emerges from the single ventricle or the rudimentary chamber. Thirteen cases belonged to group A and four to group B. The pathological structure of mitral atresia requires the decompression of the left atrium by atrioseptostomy during the neonatal period to enable survival. On a second stage a palliative correction should be carried out, which; depending on ventricular size and outlet of the vessels, will be a valvular prosthesis left atrium-left ventricle or the modified atriopulmonary technique connecting the new left atrium with the systemic ventricle and aorta after resecting the auricular septum and connecting the right atrium with the pulmonary artery.