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.

Cardiac abnormalities in the toxic oil syndrome, with comparative observations on the eosinophilia-myalgia syndrome.

Early in the course of studies of the Spanish toxic oil syndrome it was recognized that vascular lesions were a major problem, most logically attributable to endothelial damage by the toxic oil. However, most clinical attention has been directed to the pulmonary complications and the evolution into a scleroderma-like illness later. In this study of 11 victims of the toxic oil syndrome careful postmortem studies of the coronary arteries and conduction system and neural structures of the heart demonstrated major injury to all those components of the heart. Obliterative fibrosis of the sinus node in four cases resembled findings in fatal scleroderma heart disease, and in eight the cardiac lesions resembled those of lupus erythematosus. The more impressive pathologic features involved the coronary arteries and neural structures, which were abnormal in every heart. The arterial disease included widespread focal fibromuscular dysplasia, but there was also an unusual myointimal proliferative degeneration of both small and large coronary arteries in five patients, four of whom were young women. In two hearts, portions of the inner wall of the sinus node artery had actually detached and embolized downstream. Coronary arteritis was rarely found. Inflammatory and noninflammatory degeneration of cardiac nerves was widespread. Fatty infiltration, fibrosis and degeneration were present in the coronary chemoreceptor. In most respects these cardiac abnormalities resemble those described in the eosinophilia-myalgia syndrome caused by an altered form of L-tryptophan. In both diseases there is good reason to anticipate more clinical cardiac difficulties than have so far been reported, and even more basis for future concern, especially relative to coronary disease and cardiac electrical instability.

Clinical and pathologic manifestations of pulmonary vascular disease in the toxic oil syndrome.

The toxic oil syndrome in Spain affected greater than 20,000 people. In the initial stages, it was characterized by a respiratory distress syndrome with myalgias and eosinophilia. Pulmonary hypertension developed in 20% of the patients and in many, it has spontaneously regressed. Nevertheless, in a small subgroup, it has progressed to a malignant course of cor pulmonale, leading rapidly to death. Clinical and pathologic features of 40 patients with severe pulmonary hypertension due to the toxic oil syndrome are presented (32 female and 8 male patients; mean age 26 +/- 13 years). The study began in June 1981, which was near the onset of the toxic oil epidemic, and ended in December 1987, greater than 6 years later. The pulmonary hypertension is clinically and pathologically indistinguishable from primary pulmonary hypertension. Direct endothelial injury by the toxic agent is proposed as the initial trigger of this type of pulmonary hypertension, but an interaction between the toxic agent and specific individual susceptibility is probably required in its pathogenesis.

Electrophysiologic studies in atrial fibrillation. Slow conduction of premature impulses: a possible manifestation of the background for reentry.

Extrastimulus-induced intraatrial conduction delays were measured in 12 patients with documented episodes of atrial fibrillation (AF) by recording atrial electrograms at the high right atrium, His bundle region, and coronary sinus. Seventeen patients with and without heart disease, but without atrial arrhythmias served as the control group. During baseline-paced atrial rhythms, a conduction delay zone could be delineated, near the atrial effective refractory period, during which all extrastimuli produced conduction delays. When compared at the same paced cycle lengths (500 to 650 ms), the patients with AF had shorter atrial effective refractory periods (mean +/- standard deviation 206 +/- 24.1 versus 233 +/- 28.2 in control patients, p less than 0.02), wider conduction delay zones (79 +/- 21.7 ms versus 52 +/- 21 in control patients, p less than 0.01), and longer conduction delays both to the His bundle region (64 +/- 18.3 ms versus 35 +/- 21.7 in control patients, p less than 0.005) and the coronary sinus (76 +/- 18.9 ms versus 35 +/- 16.1 in control patients, p less than 0.001). Repetitive atrial responses were recorded in 6 patients with AF and in 9 control subjects. Sinus nodal function abnormalities were detected in 6 of the patients with fibrillation. Patients with AF had a higher tendency than control subjects to develop slow intraatrial conduction, as well as shorter effective refractory periods. Since both features would favor reentry, they may be the electrophysiologic manifestations of the abnormalities making these patients prone to atrial reentrant arrhythmias. Repetitive atrial responses were of no predictive value. Sinus nodal dysfunction was frequently found, but was not essential for the occurrence of AF.

Persistence of respiratory abnormalities four years after the onset of toxic oil syndrome.

We studied a random sample of 436 subjects with TOS aged 18 to 60 years, to assess the prevalence of respiratory involvement four years after onset of the syndrome. Clinical evaluation together with chest roentgenograms, electrocardiogram and functional respiratory tests were carried out. Respiratory involvement occurred in 390 (89.4 percent) individuals and was the most common abnormality detected, followed by neurological disorders in 289 (66.3 percent), osteoarticular symptoms in 171 (39.2 percent), psychiatric disorders in 96 (22 percent), hepatic involvement in 91 (20.9 percent), and sclerodermatous sequelae in 89 (20.4 percent). Among patients with respiratory involvement, dyspnea and cough were the most common complaints. Decreased VC was observed in 151 (34.6 percent) patients and reduced transfer factor of CO in 95 (21.8 percent) patients. Airway obstruction and alveolar hypoventilation were observed only in nine (2.1 percent) patients. Six (1.4 percent) patients suffered from pulmonary artery hypertension.

Pulmonary hypertension due to toxic oil syndrome. A clinicopathologic study.

Clinical and pathologic findings in seven patients who died of severe pulmonary artery hypertension due to toxic oil syndrome are assessed. These cases correspond to a late stage of evolution of the disease characterized by progressive deterioration in clinical features--increasing dyspnea, chest pain, syncope, and death (in low-output heart failure). The main pathologic pulmonary vascular findings consisted of plexiform lesions, thromboses, and venous lesions. Endothelial damage induced by the toxic agents is suggested as an initial causative mechanism, perpetuated by intimal proliferation and in situ thrombosis. Plexiform lesions appear late and active histologically. This new cause of pulmonary artery hypertension, with pathologic findings similar to those found in primary pulmonary hypertension, may help in understanding the pathophysiology of this unknown disease.

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.

[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.

[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.

[The importance of determining oxygen consumption in the indications for a heart transplant]. / Importancia de la determinación del consumo de oxígeno en las indicaciones del trasplante cardíaco.

Maximal exercise performance in patients with chronic heart failure, as determined by peak oxygen consumption (VO2max.) during exercise testing has been shown to correlate well with mortality and its use as primary determining factor in the selection of patients for heart transplant has been advocated. Patients with a VO2max of less than 14 ml/kg/min appear at particularly high risk for mortality. Exercise performance can be influenced by a number of independent factors including subject motivation, peripheral deconditioning or other intrinsic abnormalities of skeletal muscle, and primary respiratory disease. It appears to be a precise gauge of functional impairment. VO2max can be used to accurately and reproducibly place an individual in a predefined functional class.

[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.

[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.

[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.

[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.