Trends in Pulmonary Hypertension Over a Period of 30 Years: Experience From a Single Referral Centre.

INTRODUCTION AND OBJECTIVES: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, right ventricular dysfunction and death. Despite scientific advances, is still associated with high morbidity and mortality. The aim is to describe the clinical approach and determine the prognostic factors of patients with PAH treated in a national reference center over 30 years. METHODS: Three hundred and seventy nine consecutive patients with PAH (January 1984 to December 2014) were studied. Were divided into 3 periods of time: before 2004, 2004-2009 and 2010-2014. Prognostic factors (multivariate analysis) were analyzed for clinical deterioration. RESULTS: Median age was 44 years (68.6% women), functional class III-IV: 72%. An increase was observed in more complex etiologies in the last period of time: Pulmonary venooclusive disease and portopulmonary hypertension. Upfront combination therapy significantly increased (5% before 2004 vs 27% after 2010; P < .05). Multivariate analysis showed prognostic significance in age, sex, etiology and combined clinical variables as they are independent predictors of clinical deterioration (P < .05). Survival free from death or transplantation for the 1st, 3rd and 5th year was 92.2%, 80.6% and 68.5% respectively. The median survival was 9 years (95% confidence interval, 7.532-11.959) CONCLUSIONS: The PAH is a heterogeneous and complex disease, the median survival free from death or transplantation in our series is 9 years after diagnosis. The structure of a multidisciplinary unit PAH must adapt quickly to changes that occur over time incorporating new diagnostic and therapeutic techniques.

Influence of cytomegalovirus infection in the development of cardiac allograft vasculopathy after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major cause of long-term morbidity and mortality after heart transplantation (HTx), whose relationship with CMV infection is uncertain. This study evaluated the influence of CMV infection in the development of CAV. METHODS: We enrolled 166 consecutive HTx recipients who underwent their first transplant from January 1995 to July 2002. All patients received 14 days of intravenous ganciclovir and were prospectively monitored for CMV infection during the first year after HTx. CAV was diagnosed by coronary angiography performed at 1, 5, and 10 years after HTx, following the new criteria of the International Society for Heart and Lung Transplantation. We collected all variables potentially related with the development of CAV. Risk factors were studied using a complementary log-log model. RESULTS: After a median follow-up of 11 years (range, 1-17 years), 72 patients (43%) developed CAV (63.8% CAV(1), 15.2% CAV(2), 20.8% CAV(3)). Symptoms secondary to CAV were present in 32% of these patients, and 8% died because of it. In the regression multivariate analysis, independent variables associated with the development of CAV were donor age (hazard ratio [HR], 1.028; 95% confidence interval [CI], 1.002-1.053; p < 0.028), presence of cellular acute rejection ≥ 2R (HR, 1.764; 95% CI, 1.011-3.078; p < 0.0414), CMV infection (HR, 2.334; 95% CI, 1.043-5.225; p < 0.0354), and not having been treated with a calcium channel blocker (HR, 0.472; 95% CI, 0.275-0.811; p < 0.0055). CONCLUSIONS: Standardized angiographic criteria show CMV infection is associated with the development of CAV.

Pulmonary thromboendarterectomy in 106 patients with chronic thromboembolic pulmonary hypertension.

INTRODUCTION: Pulmonary thromboendarterectomy is the treatment of choice in chronic thromboembolic pulmonary hypertension. We report our experience with this technique. METHODS: Between February 1996 and June 2014, we performed 106 pulmonary thromboendarterectomies. Patient population, morbidity and mortality and the long-term results of this technique (survival, functional improvement and resolution of pulmonary hypertension) are described. RESULTS: Subjects' mean age was 53±14 years. A total of 89% were WHO functional class III-IV, presurgery mean pulmonary pressure was 49±13mmHg and mean pulmonary vascular resistance was 831±364 dynes.s.cm(-5). In-hospital mortality was 6.6%. The most important post-operative morbidity was reperfusion pulmonary injury, in 20% of patients; this was an independent risk factor (p=0.015) for hospital mortality. With a 31-month median follow-up (interquartile range: 50), 3- and 5-year survival was 90 and 84%. At 1 year, 91% were WHO functional class I-II; mean pulmonary pressure (27±11mmHg) and pulmonary vascular resistance (275±218 dynes.s.cm(-5)) were significantly lower (p<0.05) than before the intervention. Although residual pulmonary hypertension was detected in 14 patients, their survival at 3 and 5 years was 91 and 73%, respectively. CONCLUSIONS: Pulmonary thromboendarterectomy offers excellent results in chronic thromboembolic pulmonary hypertension. Long-term survival is good, functional capacity improves, and pulmonary hypertension is resolved in most patients.

High incidence of bloodstream infection due to gram-negative bacilli in patients with pulmonary hypertension receiving intravenous treprostinil.

INTRODUCTION: An excessive risk for bacteremia has recently been reported in patients with pulmonary arterial hypertension (PAH) treated with intravenous treprostinil. We aimed to assess this association in a cohort of patients from a Spanish referral center. PATIENTS AND METHODS: We performed a retrospective cohort study that included 55 patients diagnosed with PAH who received a continuous intravenous infusion of a prostanoid (epoprostenol or treprostinil) for ≥1month at our center between January 1991 and December 2011. The risk factors associated with the incidence of bacteremia were analyzed with the log-rank test. RESULTS: After a total follow-up of 64,453 treatment days, we found 12 episodes of bacteremia: Staphylococcus aureus (5 episodes), non-fermenting gram-negative bacilli (4 episodes), other gram-positive cocci (2 episodes), and Enterobacter cloacae (one episode). The incidence of bacteremia was 0.118 episodes per 1,000 treatment days in patients receiving epoprostenol versus 0.938 episodes per 1,000 treatment-days in patients receiving treprostinil (P=.0037). All episodes of bacteremia due to Gram-negative bacilli were diagnosed in patients on treprostinil. In the univariate analysis the treatment with intravenous treprostinil was associated with the incidence of bacteremia (hazard ratio: 4.09; 95% confidence interval: 1.24-14.53), although the low number of events prevented us from performing a multivariate analysis. CONCLUSIONS: Therapy with intravenous treprostinil is associated with a higher risk for bacteremia, especially due to non-fermenting Gram-negative bacilli. This association should be taken in consideration when choosing empirical antibiotic therapy for patients with PAH and sepsis.

La evolución de la hipertensión arterial pulmonar a lo largo de 30 años: experiencia de un centro de referencia / Trends in pulmonary hypertension over a period of 30 years: experience from a single referral centre

Introducción y objetivos: La hipertensión arterial pulmonar (HAP) se caracteriza por aumento de resistencias vasculares pulmonares, disfunción progresiva del ventrículo derecho y muerte. A pesar de los avances, sigue asociada a alta morbimortalidad. El objetivo del estudio es describir el tratamiento de esta enfermedad y determinar factores pronósticos de pacientes con HAP tratados en un centro de referencia nacional a lo largo de 30 años. Métodos: Se estudió a 379 pacientes consecutivos diagnosticados de HAP (enero de 1984-diciembre de 2014). Se los distribuyó en 3 intervalos de tiempo: previo a 2004, 2004-2009 y 2010-2014, y se analizaron los factores pronósticos de deterioro clínico. Resultados: La mediana de edad de los pacientes es 44 años (el 68,6% eran mujeres) y estaban en clase funcional III-IV el 72%. Se observó un incremento en etiologías más complejas: enfermedad venooclusiva e hipertensión portopulmonar en el último periodo. La terapia combinada de inicio aumentó (el 5% previo a 2004 frente al 27% posterior a 2010; p < 0,05). El análisis multivariable mostró como factores independientes de deterioro clínico edad, sexo, etiología y variables combinadas (p < 0,05). La supervivencia libre de muerte o trasplante al primero, el tercero y el quinto año fueron del 92,2, el 80,6 y el 68,5% respectivamente. La mediana de supervivencia fue 9 años (intervalo de confianza del 95%, 7,532-11,959). Conclusiones: La HAP es una enfermedad heterogénea y compleja. La mediana de supervivencia libre de muerte o trasplante en nuestra serie es 9 años. La estructura de una unidad multidisciplinaria de HAP debe adaptarse con rapidez a los cambios que se producen en el tiempo incorporando nuevas técnicas diagnósticas y terapéuticas (AU)

Introduction and objectives: Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, right ventricular dysfunction and death. Despite scientific advances, is still associated with high morbidity and mortality. The aim is to describe the clinical approach and determine the prognostic factors of patients with PAH treated in a national reference center over 30 years. Methods: Three hundred and seventy nine consecutive patients with PAH (January 1984 to December 2014) were studied. Were divided into 3 periods of time: before 2004, 2004-2009 and 2010-2014. Prognostic factors (multivariate analysis) were analyzed for clinical deterioration. Results: Median age was 44 years (68.6% women), functional class III-IV: 72%. An increase was observed in more complex etiologies in the last period of time: Pulmonary venooclusive disease and portopulmonary hypertension. Upfront combination therapy significantly increased (5% before 2004 vs 27% after 2010; P < .05). Multivariate analysis showed prognostic significance in age, sex, etiology and combined clinical variables as they are independent predictors of clinical deterioration (P < .05). Survival free from death or transplantation for the 1st, 3rd and 5th year was 92.2%, 80.6% and 68.5% respectively. The median survival was 9 years (95% confidence interval, 7.532-11.959) Conclusions: The PAH is a heterogeneous and complex disease, the median survival free from death or transplantation in our series is 9 years after diagnosis. The structure of a multidisciplinary unit PAH must adapt quickly to changes that occur over time incorporating new diagnostic and therapeutic techniques (AU)

Tromboendarterectomía pulmonar en 106 pacientes con hipertensión pulmonar tromboembólica crónica / Pulmonary Thromboendarterectomy in 106 Patients With Chronic Thromboembolic Pulmonary Hypertension

Introducción: La tromboendarterectomía pulmonar es el tratamiento de elección en la hipertensión pulmonar tromboembólica crónica. Presentamos nuestra serie completa con esta técnica. Métodos: Desde febrero de 1996 hasta junio de 2014, hemos realizado 106 tromboendarterectomías. Analizamos las características de la población, la mortalidad y morbilidad asociadas a la técnica y los resultados a largo plazo de supervivencia, mejoría funcional y resolución de la hipertensión pulmonar. Resultados: La edad media de la población fue 53 ± 14 años. El 89% estaba en clase funcional III-IV de la OMS. La presión pulmonar media prequirúrgica fue 49 ± 13 mmHg y las resistencias vasculares pulmonares 831 ± 364 dinas.s.cm-5. La mortalidad hospitalaria fue 6,6%. La morbilidad postoperatoria más relevante fue debida al edema pulmonar por reperfusión en el 20%, que fue factor de riesgo independiente (p = 0,015) para mortalidad hospitalaria. Con una mediana de seguimiento de 31 meses (rango intercuartil 50), la supervivencia a los 3 y 5 años es 90 y 84%. Al año de seguimiento, el 91% está en clase funcional I-II de la OMS, la presión pulmonar media en 27 ± 11 mmHg y las resistencias pulmonares vasculares en 275 ± 218 dinas.s.cm-5 (significativamente menores (p < 0,05) que las basales). En 14 pacientes se diagnosticó hipertensión pulmonar persistente; aun así, su supervivencia es, a los 3 y 5 años, 91 y 73%, respectivamente. Conclusiones: La tromboendarterectomía pulmonar ofrece resultados excelentes en el tratamiento de la hipertensión pulmonar tromboembólica crónica. Proporciona una elevada supervivencia a largo plazo, mejora la capacidad funcional y resuelve la hipertensión pulmonar en la mayoría de los pacientes

Introduction: Pulmonary thromboendarterectomy is the treatment of choice in chronic thromboembolic pulmonary hypertension. We report our experience with this technique. Methods: Between February 1996 and June 2014, we performed 106 pulmonary thromboendarterectomies. Patient population, morbidity and mortality and the long-term results of this technique (survival, functional improvement and resolution of pulmonary hypertension) are described. Results: Subjects' mean age was 53 ± 14 years. A total of 89% were WHO functional class III–IV, presurgery mean pulmonary pressure was 49 ± 13 mmHg and mean pulmonary vascular resistance was 831 ± 364 dynes s cm-5. In-hospital mortality was 6.6%. The most important post-operative morbidity was reperfusion pulmonary injury, in 20% of patients; this was an independent risk factor (P = .015) for hospital mortality. With a 31-month median follow-up (interquartile range: 50), 3- and 5-year survival was 90% and 84% respectively. At 1 year, 91% were WHO functional class I–II; mean pulmonary pressure (27 ± 11 mmHg) and pulmonary vascular resistance (275 ± 218 dynes s cm-5) were significantly lower (P < .05) than before the intervention. Although residual pulmonary hypertension was detected in 14 patients, their survival at 3 and 5 years was 91% and 73%, respectively. Conclusions: Pulmonary thromboendarterectomy offers excellent results in chronic thromboembolic pulmonary hypertension. Long-term survival is good, functional capacity improves, and pulmonary hypertension is resolved in most patients

Alta incidencia de bacteriemia por bacilos gramnegativos en pacientes con hipertensión pulmonar tratados con treprostinil por vía intravenosa / High Incidence of Bloodstream Infection Due to Gram-negative Bacilli in Patients With Pulmonary Hypertension Receiving Intravenous Treprostinil

Introducción: Recientemente se ha comunicado un exceso de riesgo de bacteriemia en pacientes con hipertensión arterial pulmonar (HAP) que reciben tratamiento con treprostinil intravenoso. Pretendemos evaluar esta asociación en una unidad de referencia española. Pacientes y método: Estudio de cohortes retrospectivo con inclusión de 55 pacientes con HAP seguidos en nuestro centro y que recibieron tratamiento mediante perfusión intravenosa continua con un prostanoide (epoprostenol o treprostinil) durante ≥1mes entre enero de 1991 y diciembre de 2011. Analizamos mediante el test de log-rank los factores asociados a la incidencia de bacteriemia. Resultados: Tras un seguimiento total de 64.453 días se documentaron 12 episodios de bacteriemia: Staphylococcus aureus (5 episodios), bacilos gramnegativos (BGN) no fermentadores (4 episodios), otros cocos grampositivos (2 episodios) y Enterobacter cloacae (un episodio). La incidencia de bacteriemia fue de 0,118 episodios por 1.000 días de tratamiento con epoprostenol, frente a 0,938 episodios por 1.000 días de tratamiento con treprostinil (p=0,0037). Todos los casos de bacteriemia por BGN tuvieron lugar en pacientes que recibían treprostinil. En el análisis univariante el tratamiento con treprostinil se asoció a la incidencia de bacteriemia (hazard ratio: 4,09; intervalo de confianza del 95%: 1,24-14,53), si bien el limitado número de eventos impidió la realización de un modelo multivariante. Conclusiones: El tratamiento con treprostinil intravenoso conlleva un mayor riesgo de bacteriemia, especialmente por BGN no fermentadores. Esta asociación debe ser tenida en cuenta en la elección del tratamiento antibiótico empírico en pacientes con HAP y sepsis(AU)

Introduction: An excessive risk for bacteremia has recently been reported in patients with pulmonary arterial hypertension (PAH) treated with intravenous treprostinil. We aimed to assess this association in a cohort of patients from a Spanish referral center. Patients and methods: We performed a retrospective cohort study that included 55 patients diagnosed with PAH who received a continuous intravenous infusion of a prostanoid (epoprostenol or treprostinil) for ≥1month at our center between January 1991 and December 2011. The risk factors associated with the incidence of bacteremia were analyzed with the log-rank test. Results: After a total follow-up of 64,453 treatment days, we found 12 episodes of bacteremia: Staphylococcus aureus (5 episodes), non-fermenting gram-negative bacilli (4 episodes), other gram-positive cocci (2 episodes), and Enterobacter cloacae (one episode). The incidence of bacteremia was 0.118 episodes per 1,000 treatment days in patients receiving epoprostenol versus 0.938 episodes per 1,000 treatment-days in patients receiving treprostinil (P=.0037). All episodes of bacteremia due to Gram-negative bacilli were diagnosed in patients on treprostinil. In the univariate analysis the treatment with intravenous treprostinil was associated with the incidence of bacteremia (hazard ratio: 4.09; 95% confidence interval: 1.24-14.53), although the low number of events prevented us from performing a multivariate analysis. Conclusions: Therapy with intravenous treprostinil is associated with a higher risk for bacteremia, especially due to non-fermenting Gram-negative bacilli. This association should be taken in consideration when choosing empirical antibiotic therapy for patients with PAH and sepsis(AU)

Insuficiencia cardiaca y arritmias: una interacción compleja que requiere un abordaje multidisciplinario / Heart failure and arrhythmias: a complex interaction requiring a multidisciplinary approach

La insuficiencia cardiaca es ya, y es previsible que lo sea aún más, una de las enfermedades de mayor impacto sociosanitario en los países desarrollados. Sin duda, los trastornos del ritmo asociados a insuficiencia cardiaca tienen un impacto clínico de elevada magnitud. El desarrollo científico y técnico en el abordaje de este tipo de arritmias ha sido espectacular en los últimos años y las oportunidades presentes y, previsiblemente, de futuro son muy esperanzadoras, pero es importante tener en cuenta que el éxito de cualquier abordaje terapéutico pasa por una adecuada interacción de las distintas subespecialidades cardiológicas y no cardiológicas implicadas. El abordaje multidisciplinario para esta patología es una exigencia (AU)

Today heart failure has a greater impact on public health in developed countries than the majority of diseases and its impact is likely to become even more significant in the future. Clearly, rhythm disturbances associated with heart failure have serious clinical implications. Recent years have seen dramatic scientific and technological developments in the way we approach this type of arrhythmia, and current treatment options, and those expected in the near future, are highly promising. However, it is important to remember that the success of any therapeutic approach depends on a good level of cooperation between the different cardiology subspecialties and other disciplines involved. A multidisciplinary approach to this condition is essential (AU)

Tratamiento médico en pacientes con hipertensión pulmonar tromboembólica crónica / Medical treatment in patients with chronic thromboembolic pulmonary hypertension

La tromboendarterectomía pulmonar es el tratamiento de elección en los pacientes con hipertensión pulmonar tromboembólica crónica (HPTEC). Sin embargo, hay campos en los que el tratamiento médico específico de la hipertensión pulmonar (HP) puede ser una alternativa o desempeñar un papel complementario a la cirugía. Así, en los pacientes desestimados para cirugía por obstrucción trombótica distal, los que presentan HP residual o persistente tras la cirugía y los pacientes con HP muy severa y perfil hemodinámico de alto riesgo, el tratamiento médico puede contribuir a mejorar su evolución y el resultado final de la tromboendarterectomía. Los pacientes con obstrucción distal en el árbol pulmonar y los pacientes con HP residual tras la cirugía presentan deterioro clínico y hemodinámico por la progresión de la vasculopatía pulmonar en las arteriolas de pequeño calibre. El tratamiento convencional con diuréticos, antiacoagulantes y oxigenoterapia ha demostrado escasa eficacia. En la última década, se han incorporado multitud de fármacos al tratamiento de la HP: análogos de la prostaciclina, antagonistas de los receptores de la endotelina e inhibidores de la fosfodiesterasa-5, con acción fundamental en el remodelado vascular de las arteriolas de pequeño calibre. Aunque la evidencia de su eficacia en la HP y la similitud histológica de la vasculopatía de pequeño vaso en la HPTEC con la de otras formas de HP, aportan el fundamento racional para el uso de estos fármacos en los pacientes con HPTEC, la evidencia sustentada en ensayos clínicos es todavía limitada (AU)

Pulmonary thromboendarterectomy is the treatment of choice in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, specific medical treatment of pulmonary hypertension (PH) can be an alternative or play a complementary role to surgery. Thus, in patients unsuitable for surgery due to distal thrombotic obstruction, residual or persistent PH after surgery or very severe PH and a high-risk hemodynamic profile, medical treatment may improve their clinical course and the outcome of thromboendarterectomy. Patients with distal obstruction in the pulmonary tree and those with residual PH after surgery show clinical and hemodynamic deterioration due to progression of the pulmonary vascular disease in the small caliber arterioles. Conventional treatment with diuretics, anticoagulants and oxygen therapy has been demonstrated to have little effectiveness. In the last decade, numerous drugs have been developed for the treatment of PH: prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors acting principally in vascular remodelling of small-caliber arterioles. Although evidence of the effectiveness of these drugs in PH and the histological similarity of small-vessel vasculopathy in CTEPH to that of other forms of PH provide the main rationale for the use of these drugs in patients with CTEPH, the evidence from clinical trials is still limited (AU)

Efecto del sildenafilo en un sujeto con miocardiopatía hipertrófica obstructiva candidato a trasplante cardíaco / Effect of sildenafile in patient with obstructive hypertrophic cardiomyopathy candidated to cardiac transplantation

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Valoración de la capacidad de ejercicio en los pacientes con hipertensión arterial pulmonar / Assessment of exercise functional capacity in patients with pulmonary arterial hypertension

La valoración de la capacidad funcional en los pacientes con hipertensión arterial pulmonar forma parte del protocolo diagnóstico inicial y del seguimiento. El grado de intolerancia al ejercicio tiene importantes implicaciones pronósticas y en la elección de tratamiento. Clásicamente, esta valoración se ha realizado mediante la prueba de caminata de 6 minutos. La prueba de esfuerzo cardiopulmonar, ampliamente utilizada en la disfunción ventricular izquierda, se está introduciendo como nueva herramienta en la valoración funcional de los pacientes con hipertensión arterial pulmonar, sobre todo en la de aquellos con menos limitaciones funcionales. Aparte de realizar una valoración no invasiva y objetiva de la capacidad de ejercicio, describe cuáles son los mecanismos fisiopatológicos subyacentes a dicha limitación. Es capaz también de identificar a los pacientes con cortocircuito derecha-izquierda secundario a foramen oval permeable. Tiene implicaciones pronósticas y puede emplearse para analizar la respuesta al tratamiento. Sin embargo, es compleja y requiere una gran experiencia para realizarla e interpretar sus resultados. A continuación, revisaremos el comportamiento de los pacientes con hipertensión arterial pulmonar en la prueba de esfuerzo cardiopulmonar describiendo brevemente la respuesta de nuestros pacientes y comparando los resultados con la prueba de caminata de 6 minutos.

The assessment of functional capacity is part of the diagnosisand management of patients with pulmonaryarterial hypertension. Exercise capacity impairment determines prognosis and establishes which is the besttreatment option. Practicing clinicians use various exercisemodalities in pulmonary arterial hypertension: the 6-minute walk test is the one most frequently used. Cardiopulmonary exercise testing, widely used in leftventricle dysfunction, is starting to be incorporated as anew noninvasive tool for functional assessment inpulmonary hypertensive patients, especially in those withless severe disease. Apart from providing objective information about exercise limitation it can describe the pathophysiological bases of functional impairment and it identifies patients with exercise induced right-to-leftshunt due to patent foramen ovale. Cardiopulmonary exercise testing parameters predict prognosis and assessthe response to drugs. However, it is complex and requiresgreat level of experience for interpreting its results. Thisarticle describes pulmonary hypertensive patient responseto cardiopulmonary exercise testing. Finally, we will brieflyanalyze our results comparing them with 6-minute walktest.