Central Versus Peripheral Pulmonary Embolism: Analysis of the Impact on the Physiological Parameters and Long-term Survival.

BACKGROUND: Studies aimed at assessing whether the emboli lodged in the central pulmonary arteries carry a worse prognosis than more peripheral emboli have yielded controversial results. AIMS: To explore the impact on survival and long-term prognosis of central pulmonary embolism. PATIENTS AND METHODS: Consecutive patients diagnosed with acute symptomatic pulmonary embolism by means of computed tomography (CT) angiography were evaluated at episode index and traced through the computed system of clinical recording and following-up. Central pulmonary embolism was diagnosed when thrombi were seen in the trunk or in the main pulmonary arteries and peripheral pulmonary embolism when segmental or subsegmental arteries were affected. RESULTS: A total of 530 consecutive patients diagnosed with pulmonary embolism were evaluated; 255 patients had central pulmonary embolism and 275 patients had segmental or subsegmental pulmonary embolism. Patients with central pulmonary embolism were older, had higher plasma levels of N-terminal of the prohormone brain natriuretic peptide (NT-ProBNP), troponin I, D-dimer, alveolar-arterial gradient, and shock index (P < .001 for each one). Patients with central pulmonary embolism had an all-cause mortality of 40% while patients with segmental or subsegmental pulmonary embolism (PE) had an overall mortality of 27% and odds ratio of 1.81 [confidence interval (CI) 95% 1.16-1.9]. Survival was lower in patients with central PE than in patients with segmental or subsegmental pulmonary embolism, even after avoiding confounders (P = .018). CONCLUSIONS: Apart from a greater impact on hemodynamics, gas exchange, and right ventricular dysfunction, central pulmonary embolism associates a shorter survival and an increased long-term mortality.

Prohormona N-terminal del péptido natriurético cerebral como factor predictivo de mortalidad a largo plazo después de tromboembolia pulmonar aguda / N-terminal Pro-B type natriuretic peptide as long-term predictor of death after an acute pulmonary embolism

Background and objective: After an acute pulmonary embolism few long-term prognostic factors have shown to be of practical use. We hypothesized that, as in heart failure, natriuretic peptides could serve as biomarkers of a late deleterious prognosis. Patients and methods: Consecutive patients admitted to an Internal Medicine ward diagnosed with acute pulmonary embolism were traced through the computerized system of clinical episodes of Navarra Health System and by telephone calls. On hospitalization, standard evaluation was made, previous history of cancer and cardiac disease was recorded, and N-terminal ProB-type natriuretic peptide (NT-ProBNP), D-dimer and Troponin I were measured. In the analysis all-causes death was considered. Results: Two hundred and thirty-four patients were traced, median age 75 [interquartile range (IQR) 16] years old, women 51%. At a median time of 9.5 (IQR 29) months 52 (22%) patients had died, 38 (73%) dead patients had NT-ProBNP higher than 850 ng/L. NT-ProBNP in dead patients was 2.741 (IQR 7.420) ng/L and 662 (IQR 2.517) ng/L in survivors (p < 0.001). Age (OR 4.37 CI 95% 1.04–1.16) and NT-ProBNP (OR 1.49 CI 95% 1–1.002) showed to be independent factors of mortality. Between the 3rd and 20th month after the diagnosis, a level of NT-ProBNP higher than 850 ng/L (sensitivity 0.86, specificity 0.45 and negative predictive value 0.92) was associated with a lower survival (p = 0.019), hazard ratio 1.89, OR 7.67 (CI 95% 1.52–39.44) for this period. Conclusion: Besides the unchangeable age, plasma level of NT-ProBNP measured on acute pulmonary embolism could predict longer-term all-cause death (AU)

Fundamento y objetivo: Pocos factores pronósticos se han mostrado útiles a largo plazo después de un tromboembolismo pulmonar agudo. Este estudio se realizó sobre la hipótesis de que, al igual que sucede en la insuficiencia cardiaca, los péptidos natriuréticos podrían ser útiles como biomarcadores de pronóstico adverso tardío. Pacientes y métodos: Con la ayuda del sistema informático de episodios clínicos del Sistema de Salud de Navarra y mediante llamadas telefónicas, identificamos los pacientes consecutivos ingresados en una unidad de Medicina Interna que habían sido diagnosticados de tromboembolismo pulmonar agudo. Se realizó una evaluación estándar del episodio de hospitalización y registramos los antecedentes de cáncer y cardiopatía. Asimismo, medimos los niveles de péptido natriurético NT-pro-BNP, troponina I y dímero D. Se realizó un análisis de mortalidad por todas las causas. Resultados: Identificamos 234 pacientes con una edad mediana de 75 (rango intercuartílico [RIC] 16) años, y un 51% de mujeres. Después de un período mediano de 9,5 (RIC 29) meses, 52 (22%) pacientes habían fallecido; 38 (73%) pacientes fallecidos tenían un nivel de péptido natriurético NT-pro-BNP superior a 850 ng/l. El nivel de péptido natriurético NT-pro-BNP en los pacientes fallecidos fue de 2.741 (RIC 7.420) ng/l, mientras que en los que no habían fallecido este fue de 662 (RIC 2.517) ng/l (p < 0,001). La edad (OR 4,37, IC 95% 1,04-1,16) y el péptido natriurético NT-pro-BNP (OR 1,49, IC 95% 1-1.002) fueron factores independientes de mortalidad. Entre los 3 y 20 meses después del diagnóstico, un nivel de péptido natriurético NT-pro-BNP superior a 850 ng/l (sensibilidad 0,86, especificidad 0,45 y valor predictivo negativo 0,92) se asoció a una menor supervivencia (p = 0,019), con una razón de riesgo de 1,89 y una OR de 7,67 (IC 95% 1,52-39,44) durante este período. Conclusión: Además de la edad, el nivel plasmático de péptido natriurético NT-pro-BNP determinado durante un tromboembolismo pulmonar agudo puede comportarse como un factor predictivo a largo plazo de mortalidad por todas las causas (AU)

N-terminal Pro-B type natriuretic peptide as long-term predictor of death after an acute pulmonary embolism.

BACKGROUND AND OBJECTIVE: After an acute pulmonary embolism few long-term prognostic factors have shown to be of practical use. We hypothesized that, as in heart failure, natriuretic peptides could serve as biomarkers of a late deleterious prognosis. PATIENTS AND METHODS: Consecutive patients admitted to an Internal Medicine ward diagnosed with acute pulmonary embolism were traced through the computerized system of clinical episodes of Navarra Health System and by telephone calls. On hospitalization, standard evaluation was made, previous history of cancer and cardiac disease was recorded, and N-terminal ProB-type natriuretic peptide (NT-ProBNP), D-dimer and Troponin I were measured. In the analysis all-causes death was considered. RESULTS: Two hundred and thirty-four patients were traced, median age 75 [interquartile range (IQR) 16] years old, women 51%. At a median time of 9.5 (IQR 29) months 52 (22%) patients had died, 38 (73%) dead patients had NT-ProBNP higher than 850 ng/L. NT-ProBNP in dead patients was 2.741 (IQR 7.420)ng/L and 662 (IQR 2.517)ng/L in survivors (p<0.001). Age (OR 4.37 CI 95% 1.04-1.16) and NT-ProBNP (OR 1.49 CI 95% 1-1.002) showed to be independent factors of mortality. Between the 3rd and 20th month after the diagnosis, a level of NT-ProBNP higher than 850 ng/L (sensitivity 0.86, specificity 0.45 and negative predictive value 0.92) was associated with a lower survival (p=0.019), hazard ratio 1.89, OR 7.67 (CI 95% 1.52-39.44) for this period. CONCLUSION: Besides the unchangeable age, plasma level of NT-ProBNP measured on acute pulmonary embolism could predict longer-term all-cause death.

Residual pulmonary thromboemboli after acute pulmonary embolism.

BACKGROUND: After an acute pulmonary embolism (PE), the complete resolution of thromboemboli may not be routinely achieved. The rate of persistence may depend on the time and the diagnostic technique used for evaluation. PATIENTS AND METHODS: Patients were diagnosed with acute PE by means of computed tomography angiography (CTA). While they were receiving anticoagulant therapy, a second CTA was used to explore the rate of persistence of residual thromboemboli. During the initial episode, the plasma levels of Troponin I and natriuretic peptide, patient demographics, and hemodynamic and gas exchange data were evaluated as risk factors for persistence of pulmonary thromboemboli. RESULTS: In this study 166 patients were diagnosed. A second CTA was not made in 46 (28%) patients for different reasons. In 120 (72%) patients a second CTA was made 4.5 [SD2.34] months after the initial episode (range 2-12 months). Complete clearance of thrombi occurred in 89 (74%, 95% CI 65-81) patients. Residual thrombi remained in 31 (26%, 95% CI 18-34) patients. In 6%, 13% and 81% of the patients the size of the residual thrombi was greater, similar to and smaller than initially diagnosed, respectively. The risk factors for residual thrombi included the thrombotic burden (OR 1.95), the alveolar to arterial difference of oxygen (OR 1.64), and the clinical antecedents of venous thromboembolic disease (OR 0.65). CONCLUSIONS: After 4.5 months of anticoagulant therapy, residual pulmonary thromboemboli persisted in 26% of the patients. The risk factors for residual thromboemboli include a greater initial thrombotic burden, a deeper gas exchange disturbation and a history of previous venous thromboembolism.

Utilidad clínica de la troponina I en la tromboembolia pulmonar / Clinical usefulness of troponin I in acute pulmonary embolism

Fundamento: La troponina cardíaca I (cTnI) se considera un marcador sensible de daño miocárdico en la tromboembolia pulmonar (TEP) aguda con implicaciones pronósticas, aunque los valores considerados patológicos son variables. Pacientes y método: En pacientes consecutivos con TEP objetivamente demostrada por angiografía pulmonar con tomografía computarizada (TC) helicoidal se midieron los valores de la cTnI. Los pacientes se clasificaron radiológicamente como TEP central o periférica y se clasificaron hemodinámicamente como TEP masiva, submasiva o no masiva (según las cifras de presión arterial sistólica y pro-B de péptido natriurético). Se constató el retraso diagnóstico (RD) desde el inicio de la clínica y la mortalidad a los 30 días. Resultados: Se evaluaron 164 pacientes (edad media de 70 años [desviación estándar {DE} de 15] con 76 varones [46%]). El RD fue de 5 días (diferencia intercuartílica [DIQ] de 12) (mediana de la cTnI con RD superior a 5 días de 0,003¼g/l [DIQ de 0,103] y con RD inferior a 5 días de 0,05¼g/l [DIQ de 0,096]; p< 0,05). Un valor de la cTnI superior o igual a 0,5 ocurrió en 11 pacientes (7%).Resultados: Los valores de la cTnI superiores o iguales a 0,03¼g/l se asociaron a TEP central (AUC [area under the curve área bajo la curva ] ROC [receiver operating characterisric curva de eficacia diagnóstica ] de 0,7059; intervalo de confianza [IC] del 95%: 0,6643 a 0,7475; sensibilidad de 0,75; especificidad de 0,69; valor predictivo positivo [VPP] de 0,75, y valor predictivo negativo [VPP] de 0,69) y se asociaron a TEP masiva y submasiva (AUC ROC de 0,7685; sensibilidad de 0,86; especificidad de 0,66; VPP de 0,72, y VPN de 0,82), pero no a mortalidad (AUC ROC de 0,5394). Resultados: En el análisis de regresión logística, los valores de la cTnI no fueron predictores independientes de TEP central, de TEP masiva o submasiva ni de muerte a los 30 días

Background: Troponin-I (cTp-I) is considered a sensitive biomarker of myocardial injury in acute pulmonary thromboembolism (PE) with prognosis implications, though abnormal levels vary among reports. Patients and Methods: cTp-I was measured in consecutive patients objectively diagnosed of PE by means of pulmonary angiography made with helicoidal CT. Patients were classified radiologically as central or peripheral PE and hemodynamically as massive, submassive or non-massive according to the pulmonary vessel occluded and systolic blood pressure and ProBNP levels respectively. We checked also the delay in diagnosis (DD) and 30-days all-causes mortality rate. Results: We evaluated 164 patients; the mean age was 70 (15) years, males: 76 (46%). Median DD was 5 [interquartile range (IQ) 12) days. Median cTp-I in patients with DD>5 was 0.003¼g/L (IQ 0.072)¼g/L while in patients with DD<5 was 0.05¼g/L (IQ 0.096) (p<0.05). cTp-I higher than 0.5¼g/L occurred in 11 (7%) patients. Results: Levels of cTp-I higher than 0.03¼g/L were associated with central PE, (AUROC 0.7059 CI95% 0.6643 0.7475, sensitivity 0.75, specificity 0.69, PPV 0.75 and NPV 0.69) and massive and submassive PE (AUROC 0.7685, CI95% 0.7288 0.8082 sensitivity 0.86, specificity 0.66, PPV 0.72 and NPV 0.82), but they were not associated with mortality (AUROC 0.5394).Results: In a multivariate analysis cTp-I did not show to be an independent predictor of central, massive and submassive PE or all causes death. Conclusions: In this study cTp-I was not a proper biomarker of the size of pulmonary vessel occluded, the degree of hemodynamic derangement or short-term mortality. The delay in diagnosis could influence the usefulness of cTp-I

[Clinical usefulness of troponin I in acute pulmonary embolism]. / Utilidad clínica de la troponina I en la tromboembolia pulmonar.

BACKGROUND: Troponin-I (cTp-I) is considered a sensitive biomarker of myocardial injury in acute pulmonary thromboembolism (PE) with prognosis implications, though abnormal levels vary among reports. PATIENTS AND METHODS: cTp-I was measured in consecutive patients objectively diagnosed of PE by means of pulmonary angiography made with helicoidal CT. Patients were classified radiologically as central or peripheral PE and hemodynamically as massive, submassive or non-massive according to the pulmonary vessel occluded and systolic blood pressure and ProBNP levels respectively. We checked also the delay in diagnosis (DD) and 30-days all-causes mortality rate. RESULTS: We evaluated 164 patients; the mean age was 70 (15) years, males: 76 (46%). Median DD was 5 [interquartile range (IQ) 12) days. Median cTp-I in patients with DD>5 was 0.003microg/L (IQ 0.072)microg/L while in patients with DD<5 was 0.05microg/L (IQ 0.096) (p<0.05). cTp-I higher than 0.5microg/L occurred in 11 (7%) patients. Levels of cTp-I higher than 0.03microg/L were associated with central PE, (AUROC 0.7059 CI95% 0.6643-0.7475, sensitivity 0.75, specificity 0.69, PPV 0.75 and NPV 0.69) and massive and submassive PE (AUROC 0.7685, CI95% 0.7288-0.8082 sensitivity 0.86, specificity 0.66, PPV 0.72 and NPV 0.82), but they were not associated with mortality (AUROC 0.5394). In a multivariate analysis cTp-I did not show to be an independent predictor of central, massive and submassive PE or all causes death. CONCLUSIONS: In this study cTp-I was not a proper biomarker of the size of pulmonary vessel occluded, the degree of hemodynamic derangement or short-term mortality. The delay in diagnosis could influence the usefulness of cTp-I.

N-terminal pro-B-type natriuretic peptide predicts the burden of pulmonary embolism.

BACKGROUND: In acute pulmonary embolism (PE), brain natriuretic peptides are markers of right ventricular dysfunction and they could point out the size of the occluded pulmonary vessel. METHODS: N-terminal pro-B-type natriuretic peptide (BNP) was measured in 93 consecutive outpatients diagnosed with acute PE by means of helical computed tomography. Central PE was diagnosed when thrombotic material was seen in the main trunk or right or left main branches of the pulmonary artery, and peripheral PE was diagnosed when thrombi were seen exclusively in segmental or subsegmental arteries. RESULTS: Central PE occurred in 51 (55%) patients and peripheral PE in 42 (45%). Plasma level of pro-BNP greater than 500 ng/L was independently associated with central PE. The area under the receiver operating characteristic curve was 0.753 (CI 95% 0.700-0.806), sensitivity 0.82 (CI 95% 0.69-0.91), specificity 0.67 (CI 95% 0.50-0.79), positive predictive value 0.75 (CI 95% 0.61-0.85), and negative predictive value 0.76 (CI 95% 0.58-0.87). Six (6%) patients died, 3 from PE, 2 from brain hemorrhage, and 1 from advanced gallbladder cancer. N-terminal pro-BNP level was greater than 500 ng/L in all patients who died. The area under receiver operating characteristic curve for death was 0.712 (CI 95% 0.635-0.789), sensitivity 0.10 (CI 95% 0.04-0.22), specificity 1 (CI 95% 0.88-1), positive predictive value 1 (CI 95% 0.51-1), and negative predictive value 0.42 (CI 95% 0.32-0.53). CONCLUSIONS: Preliminary data suggest that N-terminal pro-BNP levels higher than 500 ng/L could serve as indicator of the burden of PE and perhaps as a predictor of death.

Síndrome hepatopulmonar: mayoría de edad clínica / Hepatopulmonary syndrome

No disponible

[Prognostic significance of the hepatopulmonary syndrome in liver cirrhosis]. / Significado pronóstico del síndrome hepatopulmonar en la cirrosis hepática.

BACKGROUND AND OBJECTIVE: The prognosis of hepatopulmonary syndrome (HPS) has been only rarely investigated. PATIENTS AND METHOD: We investigated the survival of 32 cirrhotic patients, 14 (44%) with HPS and 18 with a normal gaseous exchange (NGE), and the associated factors. RESULTS: During a mean (standard deviation) of 56 (27) months, 9 patients in the HPS group (relative risk: 0.64) and 4 patients in the NGE group (relative risk: 0.22) died. The odds ratio was 6.42 (p < 0.01; 95% confidence interval, 0.04-0.80). Patients in the HPS group died after 44 (31) months, while patients in the NGE group died 65 (21) months after inclusion (p < 0.05). Overall, 46% of deaths were liver related. Factors associated with death were the right to left shunting and the increased plasmatic renin levels. Of note, the plasmatic volume and diffusing capacity were protective. CONCLUSIONS: The coexistence of HPS worsens the prognosis in liver cirrhosis.

Significado pronóstico del síndrome hepatopulmonar en la cirrosis hepática / Prognostic significance of the hepatopulmonary syndrome in liver cirrhosis

Fundamento y objetivo: El significado pronóstico del síndrome hepatopulmonar (SHP) se ha estudiado en pocas ocasiones. Pacientes y método: Observación de la supervivencia de 32 pacientes cirróticos, 14 (44%) de ellos con SHP y 18 con intercambio gasesoso normal (IGN), y estudio de los factores asociados. Resultados: Durante una media (desviación estándar) de 56 (27) meses fallecieron 9 pacientes (riesgo relativo de 0,64) del grupo SHP y 4 (riesgo relativo de 0,22) de los pacientes con IGN (odds ratio = 6,42; p < 0,01; intervalo de confianza del 95%, 0,04-0,80). Los pacientes con SHP fallecieron una media de 44 (31) meses tras la inclusión y los pacientes con IGN, 65 (21) meses tras la inclusión (p < 0,05). No todos los fallecimientos estuvieron relacionados con enfermedad hepática o disfunción pulmonar. Los factores asociados a mortalidad fueron el grado de shunt pulmonar y los valores plasmáticos de renina, mientras que el volumen plasmático y la capacidad de difusión de monóxido de carbono fueron factores de protección. Conclusiones: El SHP empeora el pronóstico de la cirrosis hepática

Background and objective: The prognosis of hepatopulmonary syndrome (HPS) has been only rarely investigated. Patients and method: We investigated the survival of 32 cirrhotic patients, 14 (44%) with HPS and 18 with a normal gaseous exchange (NGE), and the associated factors. Results: During a mean (standard deviation) of 56 (27) months, 9 patients in the HPS group (relative risk: 0.64) and 4 patients in the NGE group (relative risk: 0.22) died. The odds ratio was 6.42 (p < 0.01; 95% confidence interval, 0.04-0.80). Patients in the HPS group died after 44 (31) months, while patients in the NGE group died 65 (21) months after inclusion (p < 0.05). Overall, 46% of deaths were liver related. Factors associated with death were the right to left shunting and the increased plasmatic renin levels. Of note, the plasmatic volume and diffusing capacity were protective. Conclusions: The coexistence of HPS worsens the prognosis in liver cirrhosis

[Hepatopulmonary syndrome: relationship with liver dysfunction and systemic hemodynamic disorder]. / Síndrome hepatopulmonar: relación con el grado de disfunción hepática y el trastorno hemodinámico de la cirrosis hepática.

BACKGROUND AND OBJECTIVE: The hepatopulmonary syndrome (HPS) causes an increased alveolar to arterial gradient of oxygen and in advanced phases hypoxemia, as the result of pulmonary vasodilation. In liver cirrhosis, it has been demonstrated the existence of splachnic vasodilation and also in other vascular beds. Our main objectives were to know the hemodynamic status, the renal function and the condition of some humoral systems in patient diagnosed of HPS. PATIENTS AND METHOD: We studied consecutively 32 cirrhotic patients Divided in two groups, a group of 18 cirrhotic patients with normal gaseous exchange (NGE), and another group of 14 cirrhotic patients diagnosed of HPS by contrast-enhanced transthoracic echocardiography and/or lung and brain scintigraphy with 99Tc albumin macroaggregates. They were all in rest in bed, upon alcohol and tobacco abstinence and on a diet of 50 mEq of sodium. Cardiovascular drugs were all withheld during 4 days in order to reach steady state. RESULTS: Patients of the HPS group were characterized by a more advanced index of Child-Pugh and presence of clubbing and vascular spiders. They presented a greater degree of hypoxemia in a sitting position, greater hypocapnia and smaller transference factor values (TLCO). They also showed a hyperkinetic circulatory condition characterized by smaller arterial blood pressure, greater cardiac index, smaller vascular resistances and greater femoral flows, with smaller clearance of creatinine, elimination of urinary sodium, urinary volume/24 h and an increased plasmatic volume, accompanied with a greater activation of the renin-angiotensin-aldosterone axis and a greater urinary elimination of nitrites and nitrates. CONCLUSIONS: The pulmonary vasodilation that explains the HPS is a constitutive part of the systemic vasodilation occurring in liver cirrhosis, and it is related to the degree of liver dysfunction as measured by the classification of Child-Pugh. The greater activation of the renin-aldosterone system and the rise of the plasmatic volume express a highest grade of arterial underfilling caused by an increment in the nitric oxide production.