Macitentan in daily clinical practice: A single centre, 1-year experience.

The effectiveness and safety of macitentan, a dual endothelin-receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), were shown in an extensive clinical trial oriented towards morbidity and mortality events. Our aim was to describe a single centre's experience of the utilization of macitentan in patients with PAH in clinical practice settings. Thirteen patients with different aetiologies and previous PAH treatments were studied. After 12 months of macitentan treatment, 11 patients improved their functional class (FC), all patients improved their 6-minute walk distance (6MWD) test, and 10 patients lowered their NT-proBNP plasma levels. Additionally, cardiac imaging parameters were also improved. No cases resulted in hospitalization, septostomy, transplant or death.

Exploración funcional pulmonar en pacientes con hipertensión arterial pulmonar / Lung function testing in patients with pulmonary arterial hypertension

Objetivo: El objetivo principal es la descripción de los hallazgos funcionales respiratorios en una serie de 120 pacientes con hipertensión arterial pulmonar (HAP), y el objetivo secundario es su comparación con los datos hemodinámicos. Pacientes y métodos: Estudio descriptivo de la función pulmonar de los 120 casos con HAP estable, de los grupos 1 y 4 de Evian/Venecia, estudiados hasta enero de 2002 en el grupo de trabajo de Hipertensión Pulmonar y Trasplante de Pulmón del Servicio de Cardiología del Hospital Universitario 12 de Octubre de Madrid. Los datos de 47 pacientes se recogieron retrospectivamente desde 1981 a 1995, y de forma prospectiva en los 73 restantes. Se incluyeron casos de hipertensión arterial idiopática y de la asociada a colagenosis, tromboembolia pulmonar crónica, shunt cardíaco y, en 30 casos, a síndrome de aceite tóxico (SAT). Resultados: En el conjunto del grupo la capacidad vital, el volumen espiratorio forzado en el primer segundo y la capacidad pulmonar total fueron normales; los valores medios mostraron un factor de transferencia bajo (media ± desviación estándar: 67,6 ± 23,2), e hipoxemia moderada (65,8 ± 15,4 mmHg). No se observaron asociaciones significativas entre los parámetros funcionales pulmonares y los hemodinámicos. El grupo con SAT tenía la edad más baja (33,7 ± 11,4 años), junto a los valores medios más altos en la escala de la New York Heart Association (3,3 ± 0,5) y de resistencias vasculares pulmonares (20,3 ± 8,1 kPa·l­-1·s). Conclusiones: En este trabajo se estudia la función pulmonar en una serie de 120 pacientes con HAP, de los grupos 1 y 4 de Evian/Venecia, entre los que se incluyó a 30 casos con SAT. No se han encontrado asociaciones significativas entre los valores funcionales respiratorios y los hemodinámicos

Objective: The main objective was to describe the results of lung function testing in a series of 120 patients with pulmonary arterial hypertension, and the secondary objective was to compare these findings with hemodynamic variables. Patients and Methods: This was a descriptive study of lung function in 120 patients with stable pulmonary arterial hypertension (Evian/Venice groups 1 and 4) studied until January 2002 in the Pulmonary Hypertension and Lung Transplant Working Group attached to the Cardiology Department of the Hospital Universtario 12 de Octubre in Madrid, Spain. Data were collected retrospectively for the first 47 patients (1981 to 1995) and prospectively thereafter for the remaining 73 patients. The diagnosis was idiopathic arterial hypertension or hypertension associated with collagenosis, chronic pulmonary embolism, cardiac shunt, or toxic oil syndrome (30 cases). Results: In the group as a whole, forced vital capacity, forced expiratory volume in 1 second, and total lung capacity were normal; mean (SD) values revealed low carbon dioxide diffusing capacity (67.6% [23.2%]), and moderate hypoxemia (65.8 [15.4] mm Hg). No significant associations were observed between lung function and hemodynamic parameters. Mean age in the toxic oil syndrome group was lower (33.7 [11.4] years), and these patients had higher mean scores on the New York Heart Association scale (3.3 [0.5]) and for pulmonary vascular resistance (20.3 [8.1] kPa·L-­1·s). Conclusions: Lung function was studied in a series of 120 patients with pulmonary arterial hypertension (Evian/ Venice groups 1 and 4), 30 of whom had toxic oil syndrome. No significant associations were found between lung function and hemodynamic parameters

[Sildenafil as a substitute for subcutaneous prostacyclin in pulmonary hypertension]. / Sildenafilo como sustituto de prostaciclina subcutánea en la hepertensión pulmonar.

Subcutaneous prostacyclin (treprostinil) is an effective short-term treatment for pulmonary hypertension. The most frequently described adverse effect-pain in the area of injection-rarely requires that treatment be withdrawn. Sildenafil is a selective fosfodiesterase-5 inhibitor with pulmonary vasodilating effects. We describe the use of sildenafil as a substitute for treprostinil in a patient with pulmonary hypertension associated with lupus erythematosus. Treatment with treprostinil was discontinued due to uncontrollable abdominal pain.

Sildenafilo como sustituto de prostaciclina subcutánea en la hipertensión pulmonar / Sildenafil as a substitute for subcutaneous prostacyclin in pulmonary hypertension

No disponible

[Incidence and dynamic behavior of spontaneous echocardiographic contrast and atrial thrombi in the transplanted heart]. / Incidencia y comportamiento dinámico del contraste ecocardiográfico espontáneo y del trombo auricular en el corazón trasplantado.

BACKGROUND: Standard orthotopic heart transplantation produces important anatomic and functional atrial alterations with subsequent thrombotic risk. Therefore the aim of this study was to analyze the prevalence and evolution of spontaneous echocardiography, atrial thrombi and embolic events. PATIENTS AND METHOD: 52 consecutive transplanted patients were analyzed with transesophageal echocardiography and hemodynamic studies performed at 15 days and one year after transplantation. RESULTS: Spontaneous echocardiography contrast was present in 27 patients (52%). Ten atrial thrombi were observed (19.2%), 9 with spontaneous echocardiography contrast. Six atrial thrombi appeared on day 15 and 4 after one year (with spontaneous echocardiography contrast on the previous study). Using multiple logistic regression analysis left atrial size was the only independent predictor factor for spontaneous echocardiography contrast (OR = 1.27; 95% CI, 1.09-1.54) and was an important predictor factor of atrial thrombi formation (OR = 1.19; 95% CI, 1.04-1.42). Likewise, the main predictor of atrial thrombi was the presence of spontaneous echocardiography contrast (OR = 116; 95% CI, 8.4-999). The hemodynamic pattern did not predict either the presence of spontaneous echocardiography contrast or atrial thrombi. The global incidence of embolic events was 4% less than previously described. CONCLUSIONS: The incidence of atrial thrombi and spontaneous echocardiographic contrast after standard orthotopic heart transplantation was 19.2% and 52%, respectively. An enlarged atrium and/or spontaneous echocardiography contrast was found to increase the risk of atrial thrombi. Considering the dynamic nature of atrial thrombi formation, periodical transesophageal echocardiography studies are recommended after heart transplantation.

Impact of mild pulmonary hypertension on mortality and pulmonary artery pressure profile after heart transplantation.

BACKGROUND: Pulmonary hypertension is a risk factor for early mortality after transplantation, but the risk threshold is debated. Also, little is known about the evolution of pulmonary circulation after transplantation. The aim of this study was to determine the influence of current risk pulmonary pressure parameters on early post-operative mortality and to assess the time-related changes in pulmonary pressure after surgery. METHODS: One hundred twelve consecutive transplanted patients were studied retrospectively to determine the influence of trans-pulmonary gradient of >12 mm Hg and pulmonary vascular resistance of >2.5 Wood units, at baseline or after vasodilator test, on early mortality. A multivariate analysis was used to study the hemodynamic parameters associated with early mortality. The pulmonary pressures of all surviving patients were studied for up to 3 years after surgery. RESULTS: Early mortality in the groups with and without pulmonary hypertension were 24.4% and 5.6%, respectively (p =.009). The only variable that was independently associated with early mortality was the pulmonary vascular resistance index (odds ratio = 1.459). Mild pulmonary hypertension disappeared 1 year after heart transplantation. CONCLUSIONS: Mild pulmonary hypertension is a risk factor for early postoperative mortality. The hemodynamic parameter most closely associated with early mortality is pulmonary vascular resistance index. The hemodynamic profile of pulmonary circulation after heart transplantation is partially dependent on the level of pulmonary hypertension before transplantation, at least during the first year after surgery.

Manejo del enfermo con miocardiopatía dilatada y miocarditis / Management of the patient with dilated myocardiopathy and myocarditis

La miocardiopatía dilatada (MCD) es una enfermedad intrínseca del miocardio, caracterizada por la dilatación del ventrículo izquierdo o de ambos ventrículos, así como por la disminución de su contractilidad. Es más frecuente en varones en la edad media de la vida, pero debido a que en las fases iniciales suele cursar de forma asintomática, su incidencia puede estar infraestimada. Se han identificado múltiples etiologías causantes de MCD, y todo apunta a que diversos factores pueden influir conjuntamente en producirla. Con frecuencia no se encuentra el agente causal y entonces se denomina MCD idiopática. Su presentación clínica es muy variada, pero la manifestación más frecuente es la insuficiencia cardíaca (IC), que se agrava conforme evoluciona la enfermedad.El manejo de los pacientes con MCD consiste en retrasar la progresión hacia la IC y disminuir la morbimortalidad.La miocarditis es un proceso inflamatorio no isquémico del miocardio, debido a un amplio y heterogéneo grupo de agentes etiológicos con variada distribución geográfica, lo que afecta a la incidencia y prevalencia de la enfermedad. Existe una fase inicial de agresión al miocardio, que suele seguirse de curación o de una segunda fase de inflamación crónica mediada por mecanismos autoinmunes, asociados o no a la persistencia del agente causal. La clínica varía desde la curación completa hasta la evolución hacia MCD. Su tratamiento es sintomático incluyendo el manejo y prevención de las complicaciones. Actualmente se investiga con la terapia inmunosupresora, basándose en la posible perpetuación del daño miocárdico por mecanismos autoinmunes. (AU)

[An anomalous origin of the left coronary artery associated with a right coronary spasm as the cause of angina and presyncope]. / Origen anómalo de la arteria coronaria izquierda asociado a espasmo de la coronaria derecha como causa de angina y presíncope.

We describe the rare association of angina at effort and presyncope in a young patient with an anomalous origin of left coronary artery and associated coronary spasm in the normal right coronary artery. The patient did well under calcium channel blocker therapy after seven years of follow-up, which is in contrast with the usual recommended management of these patients.

[Pulmonary arterial hypertension and heart transplantation: hemodynamic evolution and survival]. / Hipertensión arterial pulmonary y trasplante cardíaco: evolución hemodinámica y supervivencia.

BACKGROUND: Patients with chronic heart failure and pulmonary arterial hypertension are at risk of developing fatal right graft failure after transplantation, and there is no agreement about the limit of pulmonary vascular resistance for such risk. PURPOSE: To study what the impact is on the survival of a degree of pulmonary hypertension not considered to be an exclusion for orthotopic heart transplantation and to analyze the hemodynamic profile in the minor circuit after surgery. PATIENTS AND METHODS: We studied a group of 69 patients consecutively transplanted and with followup of at least one year. Patients were classified in two groups depending on the hemodynamic factors previous to transplant: group A (without pulmonary hypertension, 22 patients) and group B (with pulmonary hypertension, 47 patients). After heart transplantation we analyzed the causes of mortality and the evolution hemodynamic profile in both groups. RESULTS: In the group of patients with pulmonary hypertension there was an increase in perioperative mortality due to graft failure (p < 0.05), although at the end of the first year, the survival rate was similar in both groups. After heart transplantation, the level of pulmonary pressures dropped in the same group, but at the end of the first year, a 17% of the patients maintains some criteria of pulmonary hypertension. CONCLUSIONS: Our results confirm that degrees of pulmonary hypertension classically not considered as an exclusion for orthotopic heart transplantation were associated with an increase mortality by graft failure. The majority of survivors after heart transplantation normalize pulmonary pressures at one year of transplantation.

[Pulmonary hypertension: current aspects]. / Hipertensión pulmonar: aspectos actuales.

Primary pulmonary hypertension, although less frequent than secondary forms, represents the true paradigm of this disease. The recent investigations on pulmonary vascular response mechanisms to different stimuli has increased our knowledge about the mechanism of high pulmonary pressure. Molecular biology of the endothelial cell has provided evidence that endothelial injury plus a genetic individual predisposition may be the pathogenic mainstream of this disease. The histologic findings of pulmonary hypertension are still a matter of controversy, although the clinical, epidemiological and prognostic features are better defined. Therapeutically, there has been important advances, specially with various vasodilators, like calciumantagonists, prostacyclin, adenosine and nitric oxide, as well as new routes of administration. In more advance stages of the disease, atrial septostomy (only paliative) and pulmonary or cardio-pulmonary transplantation, are other therapeutic options to consider, after an adequate selection of patients.

[Cardiomyopathies (VII). Natural history of hypertrophic cardiomyopathy]. / Miocardiopatías (VII). Historia natural de la miocardiopatía hipertrófica.

After a short historic review of conceptual developments in hypertrophic cardiomyopathy, the natural history of the disease is analyzed according to each of its morphologic and functional abnormalities. The lack of association between hypertrophic morphology and sudden death is considered. Diastolic dysfunction and LV obstruction, although a frequent cause of dyspnea and heart failure, is not a risk factor for sudden death. Something similar occurs with the infrequent appearance in this disease of contractile failure. Myocardial ischemia is frequent in hypertrophic cardiomyopathy and general prognostic information about it is still lacking. Nevertheless, in young patients with family history of sudden death, a positive Thallium effort test may be a marker of sudden death (without an arrhythmogenic substrate), and may respond to verapamil. Finally, the new knowledge about genetic mutations in hypertrophic cardiomyopathy are analized. We conclude with some futuristic comments about hypertrophic cardiomyopathy.

Prospective randomized trial of efficacy of ganciclovir versus that of anti-cytomegalovirus (CMV) immunoglobulin to prevent CMV disease in CMV-seropositive heart transplant recipients treated with OKT3.

We compared the efficacy of ganciclovir versus that of cytomegalovirus (CMV) immunoglobulin for the prevention of CMV disease in 31 CMV-seropositive heart transplant recipients who had received early immunoprophylaxis with OKT3 monoclonal antibodies. The incidence of CMV disease and visceral involvement was much higher in the CMV immunoglobulin group than in the ganciclovir group (40 versus 6%, respectively; P = 0.03). No adverse effects were found in the CMV immunoglobulin group, but 19% of the patients in the ganciclovir group developed mild leukopenia or a mild increase in their serum creatinine levels.

[Effect of 3 hypertensive++ agents on ventricular geometry and function]. / Efecto de tres antihipertensivos sobre la geometría y función ventriculares.

BACKGROUND: To assess the prevalence of left ventricular hypertrophy in hypertensive patients referred to an outpatient cardiology unit, and to assess its evolution under antihypertensive treatment. METHODS: One hundred and seven mild to moderate hypertensive patients were randomized to receive either xipamide, verapamil or atenolol. Cross-sectional echocardiography was performed in order to assess left ventricular mass and function. RESULTS: Mean age was 56 years, with a 4:1 female/male ratio. Mean follow-up was 120 days. Left ventricular hypertrophy was very common (65%) and decreased to 54% under antihypertensive treatment. Left ventricular mass decreased from 134.3 g/m2 to 118.1 g/m2 (p < 0.001). Concentric hypertrophy was the most common geometric pattern (42%), decreasing to 30% with treatment. Xipamide decreased ventricular mass by decreasing left ventricular diameters, while verapamil and atenolol decreased left ventricular thickness, mainly in septal wall. Systolic function was not modified during the treatment period. Diastolic function was not modified by xipamide and verapamil, and improved with atenolol. CONCLUSIONS: Left ventricular hypertrophy is very frequent when determined by echocardiography and all three drugs produced regression of left ventricular hypertrophy in a different way with respect to left ventricle geometry, an effect which could have potential therapeutic implications.