Clinical and hemodynamic outcomes and mortality risk factors in patients undergoing pulmonary thromboendarterectomy / Resultados clínicos y hemodinámicos y factores de riesgo de mortalidad en pacientes sometidos a tromboendarterectomía pulmonar

Abstract Background: Pulmonary thromboendarterectomy is the current treatment of choice in patients with chronic thromboembolic pulmonary hypertension. The objective of the present study was to analyze the clinical and hemodynamic outcomes and the risk factors for mortality in a cardiovascular center in Colombia. Methods: Cohort study, conducted between 2001 and 2019. All operated patients were included in the study. Risk factors associated with mortality were established by means of a multivariate regression using the COX method and survival was established using the Kaplan-Meier method. p < 0.05 was considered statistically significant. Results: Seventy-three patients were operated. Median age was 51 years, 55% of females, 79% had functional Class III and IV. The mean pulmonary arterial pressure was 50 mmHg and 640 dyn.s.cm−5 for pulmonary vascular resistance (PVR). After the intervention, there was a decrease in mean pulmonary artery pressure (p ≤ 0.001) and in PVR (p = 0.357); 21% had evidence of residual pulmonary hypertension. Only 8% and 6% continued with functional Class III and IV at 6 and 12 months, respectively. There were 15 deaths (19.1%; 12% at 30 days). The factors associated with mortality were the diastolic diameter of the right ventricle measured postoperatively (hazard ratio [HR] 10.88 95% confidence interval [CI] 1.97-62, p = 0.007), time of invasive mechanical ventilation (HR 1.06 95% CI 1.02-1.09 p = 0.004), and the presence of complications during the surgical procedure (HR 5.62 95% CI 1.94-16.22 p = 0.001). Conclusions: Pulmonary thromboendarterectomy is associated with excellent clinical and hemodynamic outcomes. The mortality risk factors found are not those usually described in the literature.

Resumen Antecedentes: La tromboendarterectomía pulmonar es el tratamiento de elección actual en pacientes con hipertensión pulmonar tromboembólica crónica. El objetivo del presente estudio fue analizar los resultados clínicos y hemodinámicos y los factores de riesgo de mortalidad en un centro cardiovascular de Colombia. Métodos: Estudio de cohorte entre 2001 y 2019. Se incluyeron todos los pacientes operados. Los factores de riesgo asociados a la mortalidad se establecieron mediante una regresión multivariante mediante el método COX y la supervivencia se estableció mediante el método de Kaplan-Meier. Los valores de p < 0.05 se consideraron estadísticamente significativos. Resultados: se operaron 73 pacientes. La mediana de edad fue de 51 años, 55% mujeres, 79% tenían clase funcional III y IV. La presión arterial pulmonar media fue de 50 mmHg y 640 dyn.s.cm−5 para la resistencia vascular pulmonar. Después de la intervención, hubo una disminución en la presión arterial pulmonar media (p ≤ 0.001) y en la resistencia vascular pulmonar (p = 0.357). El 21% tenía evidencia de hipertensión pulmonar residual. Solo el 8% y el 6% continuaron con clase funcional III y IV a los 6 y 12 meses respectivamente. Hubo 15 muertes (19.1%; 12% a los 30 días). Los factores asociados con la mortalidad fueron el diámetro diastólico del ventrículo derecho medido en el postoperatorio (HR 10.88 IC 95% 1.97-62, p = 0.007), el tiempo de ventilación mecánica invasiva (HR 1.06 IC 95% 1.02-1.09 p = 0.004) y el presencia de complicaciones durante el procedimiento quirúrgico (HR 5.62 IC 95% 1.94-16.22 p = 0.001). Conclusiones: La tromboendartectomía pulmonar se asocia con excelentes resultados clínicos y hemodinámicos. Los factores de riesgo de mortalidad encontrados no son los habitualmente descritos en la literatura.

Estudios genéticos del metabolismo de la warfarina y su utilidad en la toma de decisiones / Genetic studies of warfarin metabolism and its usefulness in decision making

Resumen Introducción: Al momento de valorar la necesidad de realizar un reemplazo quirúrgico valvular cardiaco es posible elegir entre una válvula mecánica o una bioprotésica; la elección debe tener presentes los riesgos de la terapia anticoagulante y la necesidad potencial o el riesgo de nuevas intervenciones. La anticoagulación se realiza con antagonistas de la vitamina K, y de estos, la warfarina es el que se prescribe con mayor frecuencia. Por su metabolismo hepático (P450), dicho medicamento tiene múltiples interacciones farmacológicas y no farmacológicas que en ocasiones se convierten en un verdadero problema en la práctica clínica. Hasta la fecha no se recomienda realizar de forma rutinaria una dosificación guiada por genotipo; sin embargo, se requieren estudios genéticos para definir conductas médicas cuando se hace difícil su manejo. Caso clínico: Se describe el caso de una mujer de 37 años portadora de una válvula mitral mecánica por enfermedad reumática, anticoagulada de forma crónica con warfarina; sin embargo, durante el seguimiento tuvo múltiples consultas a urgencias (entre dos y tres veces por mes) por niveles de anticoagulación en rangos subterapéuticos, como valores elevados de INR. Presentó infarto agudo de miocardio con coronarias sanas e isquemia cerebral transitoria en contexto de INR bajo, considerados así de etiología tromboembólica. Por estas dificultades se decidió realizar la medición de los niveles de factor II de la coagulación, el cual fue normal a pesar del uso del medicamento, por lo que se sospechó resistencia al fármaco. Se solicitó estudio genético que mostró genotipo asociado con actividad enzimática reducida o normal de la CYP2C9, además un genotipo WARF CYP2C9 *1/*2 y WARF VKORC1 A/A, con lo cual se concluyó que la paciente presentaba un comportamiento metabólico divergente para warfarina. Se decidió realizar un reemplazo de válvula mecánica por válvula bioprotésica, con el objetivo de suspender el uso de la warfarina. La paciente presentó una evolución clínica satisfactoria. Conclusiones: La farmacogenética ha logrado identificar polimorfismos en los genes implicados en el metabolismo de la warfarina, los cuales están relacionados con riesgo de sangrado. Estas variantes se encuentran relacionadas con los genes CYP2C9, CYP4F2 y VKORC1. Si bien no se ha demostrado un impacto clínico en los ajustes de warfarina guiados por genotipo, dichos exámenes se hacen necesarios en algunos casos para sugerir un cambio en la dosis del medicamento o su suspensión definitiva.

Abstract Introduction: When assessing the need for a cardiac valvular surgical replacement, it is possible to choose between a mechanical or bioprosthetic valve; The choice must take into account the risks of anticoagulant therapy and the potential need and/or risk of new interventions. Anticoagulation is performed with vitamin K antagonists and warfarin is the most commonly prescribed of these. This medicine due to its hepatic metabolism (P450) has multiple pharmacological and non-pharmacological interactions that sometimes become a real problem in clinical practice. To date, it is not recommended to routinely perform a genotype-guided dosage. However, such genetic studies are necessary to define medical behaviors when handling is difficult. Case report: It is described a case of a 37-year-old woman with a mechanical mitral valve due to rheumatic disease, chronically anticoagulated with warfarin; however, during the follow-up with multiple emergency consultations (2-3 times per month) for anticoagulation levels in subtherapeutic ranges such as elevated INR levels. She presented acute myocardial infarction with healthy coronary arteries and transient cerebral ischemia in the context of low INR thus considered thromboembolic etiology. Due to these difficulties, it was decided to measure coagulation factor II levels, which was normal despite the use of the drug, suspecting drug resistance. A genetic study was requested that showed genotype associated with reduced or normal CYP2C9 enzymatic activity, plus a WARF CYP2C9 * 1/* 2 and WARF VKORC1 A/A genotype concluding that the patient presented a divergent metabolic behavior for warfarin. It was decided to perform a mechanical valve replacement with a bioprosthetic valve, in order to suspend the use of warfarin. The patient presented a satisfactory clinical evolution. Conclusions: Pharmacogenetics has managed to identify polymorphisms in the genes involved in warfarin metabolism, which are related to bleeding risk. These variants are related to the CYP2C9, CYP4F2 and VKORC1 genes. Although no clinical impact has been demonstrated in genotype-guided warfarin adjustments, such tests are necessary in some cases to suggest a change in the dose of the medication or the definitive suspension.

Clinical and hemodynamic outcomes and mortality risk factors in patients undergoing pulmonary thromboendarterectomy.

BACKGROUND: Pulmonary thromboendarterectomy is the current treatment of choice in patients with chronic thromboembolic pulmonary hypertension. The objective of the present study was to analyze the clinical and hemodynamic outcomes and the risk factors for mortality in a cardiovascular center in Colombia. METHODS: Cohort study, conducted between 2001 and 2019. All operated patients were included in the study. Risk factors associated with mortality were established by means of a multivariate regression using the COX method and survival was established using the Kaplan-Meier method. p < 0.05 was considered statistically significant. RESULTS: Seventy-three patients were operated. Median age was 51 years, 55% of females, 79% had functional Class III and IV. The mean pulmonary arterial pressure was 50 mmHg and 640 dyn.s.cm-5 for pulmonary vascular resistance (PVR). After the intervention, there was a decrease in mean pulmonary artery pressure (p ≤ 0.001) and in PVR (p = 0.357); 21% had evidence of residual pulmonary hypertension. Only 8% and 6% continued with functional Class III and IV at 6 and 12 months, respectively. There were 15 deaths (19.1%; 12% at 30 days). The factors associated with mortality were the diastolic diameter of the right ventricle measured postoperatively (hazard ratio [HR] 10.88 95% confidence interval [CI] 1.97-62, p = 0.007), time of invasive mechanical ventilation (HR 1.06 95% CI 1.02-1.09 p = 0.004), and the presence of complications during the surgical procedure (HR 5.62 95% CI 1.94-16.22 p = 0.001). CONCLUSIONS: Pulmonary thromboendarterectomy is associated with excellent clinical and hemodynamic outcomes. The mortality risk factors found are not those usually described in the literature.

Arterial lactate levels and their prognostic value in patients undergoing pulmonary thromboendarterectomy.

Objective: Evaluate the change of lactate levels and its prognostic role in the postoperative period of patients undergoing pulmonary thromboendarterectomy. Methods: Retrospective study between 2001 and 2019. Patients older than 18 years and who underwent pulmonary thromboendarterectomy were included. The U Mann Whitney test was performed to evaluate the change between lactate levels, and Cox regression analysis to evaluate the relationship with mortality. Areas under the curve were constructed for lactate levels. Results: Seventy-three patients were operated on during the study period. Median age was 51 years, 55% female. The median lactate on days 1 was 4.65 mml/L and on day 2 it was 1.62 mml/L with a change of 2.87 mml/L. No differences were found between the levels measured on day 1 and 2 between the people who died and those who did not on day 30. In the multivariate regression of COX, no relationship with mortality was found. The area under the curve shows regular performance on both day 1 and day 2 in predicting mortality outcomes. Conclusions: The behavior of the lactate in patients undergoing pulmonary thromboendarterectomy shows a rapid change during the first hours after the procedure. No role was found as a predictor of mortality neither in-hospital nor in follow-up.

Objetivo: Evaluar el cambio de los niveles de lactato y su rol pronóstico en el posoperatorio de pacientes sometidos a tromboendarterectomía pulmonar. Métodos: Estudio retrospectivo entre 2001 y 2019. Se incluyeron pacientes mayores de 18 años que fueron sometidos a tromboendarterectomía pulmonar. Para evaluar el cambio entre los niveles de lactato se realizó la prueba de U Mann Whitney. Para evaluar la relación con la mortalidad se realizó un análisis multivariado de Cox. Se construyeron áreas bajo la curva para los niveles de lactato. Resultados: . Setenta y tres pacientes fueron operados durante el período de estudio. La mediana de edad fue de 51 años, 55% mujeres. La mediana de lactato en el día 1 fue de 4,65 mmL/L y en el día 2 fue de 1,62 mmL/L con un cambio de 2,87 mmL/L. No se encontraron diferencias entre los niveles medidos el día 1 y 2 entre las personas que murieron y las que no al día 30 hospitalario. En la regresión multivariada de COX no se encontró relación con la mortalidad. El área bajo la curva muestra un desempeño regular tanto en el día 1 como en el día 2 para predecir el resultado de la mortalidad en especial intrahospitalaria. Conclusiones: El comportamiento del lactato en pacientes sometidos a tromboendarterectomía pulmonar muestra un cambio rápido durante las primeras horas posteriores al procedimiento. No se encontró que sea un predictor de mortalidad ni hospitalaria ni durante el seguimiento.

Impacto de COVID-19 en la enfermedad cardiovascular / Impact of COVID-19 on cardiovascular disease

Resumen La enfermedad por coronavirus-2019 (COVID-19) es una enfermedad infecciosa cuya sintomatología inicial, en la mayoría de las ocasiones, se manifiesta con compromiso del tracto respiratorio. El virus que causa dicha enfermedad se denomina síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV2). Si bien la manifestación grave más frecuente de la infección parece ser la neumonía, se han documentado diversas implicaciones cardiovasculares. Las personas que cursan con dicha infección y que tienen una enfermedad cardiovascular preexistente tienen un riesgo mayor de cuadros graves y mortalidad. Existen asociaciones directas o indirectas de la infección con injuria miocárdica, arritmias, enfermedad tromboembólica venosa y miocarditis. Los tratamientos en investigación pueden tener efectos adversos en el sistema eléctrico del corazón; además, algunos medicamentos de uso crónico (como los inhibidores del sistema renina angiotensina aldosterona) se les ha otorgado un polémico papel en la virulencia del microorganismo. La alta demanda en atención en salud que requieren los pacientes infectados por SARS-CoV 2 puede comprometer la asistencia de pacientes cardiovasculares sin dicha infección y dejar en riesgo de exposición al personal sanitario. Se presenta una revisión sobre los aspectos más llamativos donde estas dos condiciones interaccionan.

Abstract Coronavirus-2019 disease (COVID-19) is an infectious disease which initial symptoms, in most cases, manifest with respiratory tract compromise. The virus that causes said disease is called severe acute respiratory syndrome by coronavirus 2 (SARS-CoV 2), although the most frequent serious manifestation of the infection appears to be pneumonia, various implications have been documented from the cardiovascular point of view. People who have this infection and a pre-existing cardiovascular disease have an increased risk of severe symptoms and mortality. There are direct or indirect associations of the infection with myocardial injury, arrhythmias, venous thromboembolic disease and myocarditis. Investigational treatments may have adverse effects on the heart's electrical system. In addition, some medications of chronic use (such as renin angiotensin aldosterone systeminhibitors), have been given a controversial role in the virulence of the organism. The high demand in health care required by patients infected with SARS-CoV 2 can compromise the care of cardiovascular patients without said infection, in addition to leaving healthcare personal at risk of exposure. Therefore, a review is presented on the most striking aspects where these two conditions interact.

[High-risk electrocardiographic patterns in Patients with acute coronary syndrome]. / Patrones electrocardiográficos de alto riesgo en pacientes con síndrome coronario agudo.

Acute myocardial infarction is the leading cause of death in the world and the electrocardiogram remains the diagnostic tool for determining an acute myocardial infarction with ST-segment elevation. In spite of this, only half of the patients present classic electrocardiogram findings compatible with the ST-elevation infarction criteria. There is a spectrum of electrocardiographic findings that may reflect a phenomenon of acute coronary occlusion, which should be promptly recognized by the clinician to offer early reperfusion therapy.

[Coronary chronic total occlusion and bifurcation lesions, lessons from contemporary management: case report]. / Oclusión crónica total coronaria y lesiones en bifurcaciones, lecciones del manejo contemporáneo: reporte de caso.

Coronary artery disease involving chronic occlusions and bifurcation lesions continues to be a challenge for the interventional cardiologist. The improvement in the techniques has allowed a higher success rate, however, the best intervention strategy is unknown in this subgroup of patients with chronic occlusions and associated bifurcation lesions. We present the case of a patient in whom, in an angiography for study of chest pain, a chronic total occlusion and a bifurcation lesion were evidenced and were successfully treated by coronary intervention.

[Heart Failure With Preserved Ejection Fraction: A Problem Of Contemporary Cardiology]. / Falla Cardíaca con Fracción de Eyección Preservada: Un Problema de la Cardiología Contemporánea.

Heart failure with preserved ejection fraction (HFpEF) is a frequent and overlooked medical condition that represents a great challenge for diagnosis and treatment. Current data shows a temporal trend towards a higher prevalence of HFpEF, even above heart failure with reduced ejection fraction (HFrEF). The pathophysiology of HFpEF is heterogeneous and involves several factors such as genetics, lifestyle, and cardiac and non-cardiac comorbidities. These factors result in remodeling, maladaptation and cardiac stiffness, that later on cause dyspnea, exercise intolerance, and fatigue. Although the mortality outcome of HFpEF is as high as HFrEF, no specific therapy has demonstrated overall benefit in these patients; which is why future therapies will bet on an individualized approach according to the patients phenotype.

La persistencia de delirium a los 3 meses del egreso de los pacientes ancianos hospitalizados en una clínica universitaria / Persistent Delirium in Elderly patients Three Months After Hospital Discharge from a University Clinic

RESUMEN Objetivos: El delirium es muy prevalente entre los pacientes ancianos con enfermedad general. Si no se revierte en el momento del alta hospitalaria, se lo considera «delirium persistente¼ (DP). El propósito del estudio es describir la prevalencia y las características de los pacientes con DP 3 meses después del egreso hospitalario de la Clínica Universitaria Bolivariana (CUB). Métodos: Se realizó un estudio descriptivo longitudinal para evaluar la prevalencia y las características de los pacientes de 65 o más arios del servicio de hospitalización de la CUB que cumplieran criterios de delirium del DSM-5 al ingreso, el egreso y 3 meses después. Se determinaron las variables sociodemográficas y se aplicaron las escalas CGI-S y DRS-R98. Resultados: Se evaluó a 30 pacientes con diagnóstico de delirium con interconsulta por psiquiatría de enlace entre abril y octubre de 2013, y se excluyó a 6 por no cumplir los criterios de inclusión. Se incluyó en el estudio a 24 pacientes, de los que 9 fallecieron durante la hospitalización (37,5%). De los 15 sobrevivientes, 5 (el 20,8% de la muestra) presentaron remisión del delirium al egreso y 10 (41,6%) continuaron con síntomas y conformaron el grupo de DP. Del grupo de DP, 5 (20,8%) presentaron DP completo y los otros 5 (20,8%), DP subsindrómico (DPSS). A los 3 meses del egreso, solo 2 pacientes (8,3%) continuaron con DP completo y otros 2 (8,3%), con DPSS. En el grupo de pacientes con DP, la prevalencia fue del 30% (diagnóstico de delirium al ingreso) y una incidencia del 70% (aparición del delirium durante la hospitalización). Conclusiones: Un grupo importante de pacientes con delirium continúan sintomáticos 3 meses después del alta. El 40% de los pacientes con síntomas persistentes en el seguimiento a 3 meses indica una trayectoria de mejoría gradual del delirium, lo cual tiene implicaciones en la práctica clínica.

ABSTRACT Objective: The purpose of the study was to determine the prevalence and characteristics of patients with persistent delirium (PD) at three months after hospital discharge. Methodology: Longitudinal descriptive study to assess the prevalence and characteristics of in-patients aged 65 years and older in the Clinica Universitaria Bolivariana who met DSM-5 criteria for delirium at admission, at discharge, and at a 3-month follow up assessment. Socio-demographic features were determined, and CGI-S and DRS-R98 scales used. Results: A total of 30 patients were evaluated between April and October 2013, but 6 did not fulfil the inclusion criteria. The study included 24 patients, with 9 (37.5%) dying during hospitalisation. Of the 15 surviving patients, five (20.8% of the total sample) had their delirium resolved at discharge, and ten (41.6% of the sample) continued with symptoms. These established the PD group, of whom five of them (20.8%) had full PD, and the other five (20.8%) sub-syndromal PD (SSPD). At the final assessment, only two patients (8.3%) continued with full PD, and another two (8.3%) with SSPD. Among the PD group, 30% had a full delirium at admission (prevalence), and 70% developed full delirium during hospitalization (incidence). Conclusions: A significant number of patients did not recover from delirium at leaving hospital, and remained symptomatic three months after discharge. The study findings suggest a course of gradual improvement of delirium, with a persistence of symptoms over time in 40% of the patients, which would have implications for the clinical practice.

Persistent Delirium in Elderly patients Three Months After Hospital Discharge from a University Clinic. / La persistencia de delirium a los 3 meses del egreso de los pacientes ancianos hospitalizados en una clínica universitaria.

OBJECTIVE: The purpose of the study was to determine the prevalence and characteristics of patients with persistent delirium (PD) at three months after hospital discharge. METHODOLOGY: Longitudinal descriptive study to assess the prevalence and characteristics of in-patients aged 65 years and older in the Clinica Universitaria Bolivariana who met DSM-5 criteria for delirium at admission, at discharge, and at a 3-month follow up assessment. Socio-demographic features were determined, and CGI-S and DRS-R98 scales used. RESULTS: A total of 30 patients were evaluated between April and October 2013, but 6 did not fulfil the inclusion criteria. The study included 24 patients, with 9 (37.5%) dying during hospitalisation. Of the 15 surviving patients, five (20.8% of the total sample) had their delirium resolved at discharge, and ten (41.6% of the sample) continued with symptoms. These established the PD group, of whom five of them (20.8%) had full PD, and the other five (20.8%) sub-syndromal PD (SSPD). At the final assessment, only two patients (8.3%) continued with full PD, and another two (8.3%) with SSPD. Among the PD group, 30% had a full delirium at admission (prevalence), and 70% developed full delirium during hospitalization (incidence). CONCLUSIONS: A significant number of patients did not recover from delirium at leaving hospital, and remained symptomatic three months after discharge. The study findings suggest a course of gradual improvement of delirium, with a persistence of symptoms over time in 40% of the patients, which would have implications for the clinical practice.