Machine Learning for Short-Term Mortality in Acute Decompensation of Liver Cirrhosis: Better than MELD Score.

Prediction of short-term mortality in patients with acute decompensation of liver cirrhosis could be improved. We aimed to develop and validate two machine learning (ML) models for predicting 28-day and 90-day mortality in patients hospitalized with acute decompensated liver cirrhosis. We trained two artificial neural network (ANN)-based ML models using a training sample of 165 out of 290 (56.9%) patients, and then tested their predictive performance against Model of End-stage Liver Disease-Sodium (MELD-Na) and MELD 3.0 scores using a different validation sample of 125 out of 290 (43.1%) patients. The area under the ROC curve (AUC) for predicting 28-day mortality for the ML model was 0.811 (95%CI: 0.714- 0.907; p < 0.001), while the AUC for the MELD-Na score was 0.577 (95%CI: 0.435-0.720; p = 0.226) and for MELD 3.0 was 0.600 (95%CI: 0.462-0.739; p = 0.117). The area under the ROC curve (AUC) for predicting 90-day mortality for the ML model was 0.839 (95%CI: 0.776- 0.884; p < 0.001), while the AUC for the MELD-Na score was 0.682 (95%CI: 0.575-0.790; p = 0.002) and for MELD 3.0 was 0.703 (95%CI: 0.590-0.816; p < 0.001). Our study demonstrates that ML-based models for predicting short-term mortality in patients with acute decompensation of liver cirrhosis perform significantly better than MELD-Na and MELD 3.0 scores in a validation cohort.

Successful utilization of nirmatrelvir/ritonavir and dexamethasone in a patient with total artificial heart and COVID-19: A case report.

RATIONALE: Management of coronavirus disease 2019 (COVID-19) has been the subject of extensive research and study, leading to the development of strategies and treatments. Nonetheless, there remains a dearth of information concerning patients who require mechanical circulatory system support. This case report presents one of the first documented cases of successful utilization of nirmatrelvir/ritonavir (Paxlovid) and dexamethasone in the treatment of a patient with a total artificial heart. PATIENT CONCERNS: The patient in this case study was a 28-year-old male who had been experiencing severe heart failure. In need of a heart transplant, he underwent a procedure for implantation of a total artificial heart as a bridge to transplantation. DIAGNOSES: Unfortunately, after the surgical intervention, the patient contracted COVID-19, as confirmed by polymerase chain reaction. INTERVENTIONS: The therapeutic approach involved a 5-day regimen of nirmatrelvir/ritonavir at a dosage of 300/100 mg administered twice daily, along with a daily dosage of 6 mg of dexamethasone. OUTCOMES: Remarkably, the patient oxygenation level improved on the second day of therapy. Consequently, he was transferred from the intensive care unit to the general floor. After 71 days with the total artificial heart, the patient successfully underwent heart transplantation. LESSONS: This case report provides a compelling example of the successful application of nirmatrelvir/ritonavir and dexamethasone in the treatment of a COVID-19 patient with a total artificial heart. The positive outcome observed in this case underscores the potential use of these therapeutic agents in this specific patient population. However, it is imperative to conduct further research to corroborate and validate these initial findings. This study lays the foundation for further exploration of the efficacy of these drugs in patients with mechanical circulatory support systems.

Case Report: COVID-19 Infection of a Transplanted Heart Simulating Cellular Rejection.

Contemporary reports showed that solid organ transplantation patients who contract SARS-CoV-2 infection have a high mortality rate. There are sparse data about recurrent cellular rejections and the immune response to the SARS-CoV-2 virus in patients after heart transplantation. Herein, we report a case of a 61-year-old male post-heart transplant patient who tested positive for COVID-19 and developed mild symptoms 4 months after transplantation. Thereafter, a series of endomyocardial biopsies showed histologic features of acute cellular rejection despite optimal immunosuppression, good cardiac functions, and hemodynamic stability. Demonstration of SARS-CoV-2 viral particles by electron microscopy in the endomyocardial biopsy confirmed the presence of the virus in the foci of the cellular rejection, pointing to a possible immunologic reaction to the virus. To our knowledge, there is limited information regarding the pathology of COVID-19 infection in immunocompromised heart transplant patients, and there are no well-established guidelines for treating such patients. Based on the demonstration of SARS-CoV-2 viral particles within the myocardium, we concluded that myocardial inflammation visible on endomyocardial biopsy might be attributed to the host's immune response to the virus, which mimics acute cellular rejection in newly heart transplanted patients. We report this case to increase awareness of such events post-transplantation and to add to knowledge regarding the management of patients with ongoing SARS-CoV-2 infection that proved to be challenging.

Successful heart transplantation from a donor with bacterial and fungal bloodstream infection: Case report of donor optimization strategy.

Donor optimization is vital to increase donor hearts utilized for transplantation. We report a case of a 34-year-old female with end-stage cardiomyopathy that was admitted to the intensive care unit on inotropic support with progressive decline (INTERMACS-2). She was offered a donor heart from a 14-year male that was found to have Klebsiella pneumoniae bacteremia and candidemia co-infection. The donor was transferred to our hospital and optimized hemodynamically and biochemically. Targeted antimicrobial and antifungal therapy based on the susceptibility testing was established in the donor till blood cultures were negative. The recipient received similar prophylactic therapy for 2-week course starting 24-h before transplantation. The patient was transplanted with no clinical consequences. She was discharged home in 4 weeks post-transplantation. Her 3-month follow-up was completely uneventful.

Impact of Vitamin D Supplementation on Bone Mineral Density and All-Cause Mortality in Heart Transplant Patients.

Vitamin D (VD) deficiency is frequently reported in heart transplant (HT) recipients and routinely supplemented. However, the efficacy of VD supplementation on bone mineral density (BMD) and its association with all-cause mortality is underinvestigated. The VD levels and BMD were studied for two years, and the association of VD and BMD with all-cause mortality risk was investigated. Ninety-six HT patients (38.18 ± 12.10 years old; 74% men) were followed up during VD, Ca, and Mg supplementation. Anthropometric measurements, BMD by Dual-energy X-ray absorptiometry (DEXA) scan, VD concentrations, and related biochemical parameters were analyzed before, 1 year, and 2 years after HT. Despite significant improvement of VD3 and 25-hydroxy VD (25OHVD) levels especially in the men, BMD parameters were insignificantly changed. After 2 years, the all-cause mortality rate was 15.6%. High pretransplant levels of 25OHVD failed to improve the survival probability. Cox's regression showed a 32.7% increased hazard ratio for each unit increase in body mass index (95% CI: 1.015-1.733, p = 0.038), in the VD-deficient group rather than in the VD-sufficient one. In conclusion, VD supplementation improves the biochemical status, especially in VD-deficient HT. However, its impact on the BMD and mortality was not as usually expected. Further investigation of the disturbed VD metabolism in HT is warranted.

Deactivation of left ventricular assist device (LVAD) after recovery of cardiac function: A case report.

Recovery of heart function during support with a durable left ventricular assist device (LVAD) is uncommon. There are few reports of cases that address eliminating the LVAD without the need for a heart transplant. Radical surgical removal of the LVAD may distort the left ventricular cavity and thus affect its function, in addition to the associated risks of the operation. Innovative ways to deactivate the LVAD, relying mainly on vascular plugs implanting in the outflow graft, have been used. Few reports have shown the success of this method. In this case report, we review the story of a young patient with advanced heart failure who underwent LVAD implantation. After six months, there was a dramatic improvement of heart function that enabled successful deactivation of the device.

Donor-specific HLA-DQ antibodies may contribute to poor graft outcome after heart transplantation.

BACKGROUND: HLA-DQ donor-specific antibodies (DSA) are implicated in allograft dysfunction after renal and lung transplantation. Limited data exists on the impact of HLA-DQ antibodies on heart transplant patients. OBJECTIVE: To investigate the impact of DSA formation on allograft function and outcomes in heart transplant patients. DESIGN: Retrospective cohort study. SETTING: Collating post-transplantation patient data from computerized database in a tertiary hospital in Riyadh, Saudi Arabia from January 2006 to October 2014. PATIENTS AND METHODS: We excluded recipients with positive preoperative complement-dependent-cytotoxicity crossmatch grafts and those with preformed DSA. Anti-HLA antibodies were identified using Luminex-based assay in sera collected before transplantation with a routine endomyocardial biopsy the first year and then annually. MAIN OUTCOME MEASURES: Primary outcome measures were all-cause mortality, development of antibody mediated rejection, treated acute cellular rejection (ACR) and cardiac allograft vasculopathy (CAV). SAMPLE SIZE: 127 patients. RESULTS: DSA formation occurred in 43/127 (34%), with 33/43 (77%) targeting HLA-DQ antigens alone (n=7) or in combination with -DR, -A or B antibodies (n=26). Most (76%) were male and the mean (SD) age was 36 (14) years. Ten patients developed -A, -B or -DR antibodies without -DQ antibodies also present. Treated ACR (P=.011), reduced left ventricular ejection fraction (P less than .001), CAV development (P=.003), and all-cause mortality (P=.01) were all significantly more prevalent in the DSA-positive cohort. CONCLUSION: HLA-DQ donor-specific antibodies were the most common type detected and may play a significant role in poor outcomes post-cardiac transplantation. This emphasizes the importance of HLA-DQ matching and monitoring for DSA formation in order to minimize post-transplantation immunological risk. LIMITATIONS: Retrospective design comes with inherent biases, results from single institute, with a particularly young cohort. CONFLICT OF INTEREST: None.

Cytomegalovirus infection and disease reduce 10-year cardiac allograft vasculopathy-free survival in heart transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. METHODS: A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. RESULTS: Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infection (6.7 years; 95 % CI, 6.0-7.4) compared with CMV disease (4.2 years; CI, 3.2-5.2; p < 0.001) or asymptomatic CMV infection (5.4 years; CI, 4.3-6.4; p = 0.013). In univariate analysis, recipient age, donor age, coronary artery disease (CAD), asymptomatic CMV infection and CMV disease were significantly associated with CAV-free survival. In multivariate regression analysis, CMV disease, asymptomatic CMV infection, CAD and donor age remained independent predictors of CAV-free survival at 10 years post-transplant. CONCLUSIONS: CAV-free survival was significantly reduced in patients with CMV disease and asymptomatic CMV infection compared to patients without CMV infection. These findings highlight the importance of close monitoring of CMV viral load and appropriate therapeutic strategies for preventing asymptomatic CMV infection.

Tricuspid regurgitation influences outcome after heart transplantation.

BACKGROUND: We investigated the correlation between tricuspid regurgitation (TR) and late survival, and its relation to bicaval (BC) and biatrial (BA) technique, after heart transplantation (HTx). METHODS: HTx was performed in 464 patients between 1984 and 2009 at Sahlgrenska University Hospital. The BA technique was mostly performed in the early experience and BC in the late experience. Most patients underwent echocardiograms, and data for TR were retrospectively gathered at discharge and at the 5-year and 10-year follow-up. Survival with regard to surgical technique and to post-operative TR was analyzed. RESULTS: The BC technique resulted in less early TR (p < 0.001). This difference was still observed among survivors at 5 years (p = 0.013) but not at 10 years (p = 0.082). A multivariate logistic regression analysis found the BA technique was the only predictor of early moderate to severe TR (odds ratio, 2.70; 95% confidence interval, 1.68-4.32; p < 0.001). Furthermore, when time era was introduced, it became the only significant predictor, with a lower risk to develop moderate to severe early post-operative TR in more recent eras. There was no significant difference in long-term survival between the 2 surgical technique groups. However, stratified for TR at discharge, patients with mild or no TR had better survival than those with moderate or severe TR (p < 0.01). CONCLUSIONS: The BC technique results in less TR early post-operatively. The BA technique and/or time era seem to predict the occurrence of early moderate to severe TR. Regardless of the technique used, patients with moderate or severe TR at discharge have an increased mortality during the first 5 years.

Pressure reflection in the pulmonary circulation by echocardiography in patients with left heart disease indicates reactive pulmonary hypertension.

OBJECTIVES: The two hemodynamic profiles in left heart disease (LHD) with pulmonary hypertension (PH), passive PH with increased pulmonary venous pressure and reactive PH with increased pulmonary vascular resistance (PVR > 3 Wood units, WU), are difficult to distinguish non-invasively. We hypothesized that echocardiographic signs of pressure reflection (PR) in the pulmonary circulation can be used to diagnose reactive PH. MATERIAL AND METHODS: The study comprised 122 patients divided into three groups: patients without PH (No PH, n = 61), patients with LHD, PH and normal PVR (passive PH, n = 29) and patients with LHD, PH and increased PVR (reactive PH, n = 32). Echocardiography and right heart catheterization were performed within 24 h. Three parameters were selected related to PR [the acceleration of flow in the right ventricular outflow tract (RVOT), the interval and the augmentation of pressure between peak RVOT flow and peak RV pressure]. Cutoff values aiming at ruling in (high positive likelihood ratio, PLR) and ruling out (low negative likelihood ratio, NLR) increased PVR were determined using receiver operator characteristic (ROC) curves. RESULTS: The proportions of the patients with PH and PVR > 3 WU were 50% and 29%. Twenty-one percent had both increased pulmonary capillary wedge pressure and PVR. The area under the ROC curve for the PR parameters was 0.82-0.89. The PLR with ruling in cutoff values ranged from 4.7 to 9.4. The NLR with ruling out cutoff values ranged from 0.20 to 0.12. CONCLUSIONS: Echocardiographic assessment of PR in patients with LHD can be used to identify or exclude reactive PH.

Right ventricular ejection fraction during exercise as a predictor of mortality in patients awaiting lung transplantation: a cohort study.

OBJECTIVE: The occurrence of right ventricular dysfunction is a well-known indicator of poor prognosis in patients with chronic cardiopulmonary disease. The role of right ventricular ejection fraction (RVEF) at rest and during exercise as predictors of outcome in patients awaiting lung transplantation (LTx) is unclear. DESIGN: We performed a retrospective analysis of lung transplant candidates who had undergone equilibrium radionuclide angiography (ERNA), to determine baseline and exercise RVEF. Lung function, gas exchange and pulmonary haemodynamics were also assessed. PATIENTS AND MAIN OUTCOME MEASURES: 152 patients (mean age 47±11 years; 59% women) were included in the study. Primary endpoint was death on the waiting list for LTx. Main diagnoses were α-1 antitrypsin deficiency (n=35), chronic obstructive pulmonary disease (n=41), cystic fibrosis (n=10), interstitial lung disease (n=34) and pulmonary arterial hypertension (n=32). Twenty-five patients died (16, 4%). LTx was performed in 121 patients. The mean RVEF at rest was equal to mean RVEF during exercise (38±12%). In univariate analysis RVEF at rest, RVEF during exercise, heart rate and forced volume capacity (FVC) % of predicted were factors significantly associated with risk of death. In multivariate analysis RVEF during exercise and FVC% of predicted were independent predictors of death. CONCLUSIONS: In lung transplant candidates, right ventricular function during exercise is a stronger predictor of outcome than right ventricular function at rest. RVEF during exercise assessed by ERNA could be incorporated into priority-based allocation algorithms for LTx.

Can pulmonary hypertension and increased pulmonary vascular resistance be ruled in and ruled out by echocardiography?

BACKGROUND: Several treatment options are available for pulmonary vascular disease, and more patients are considered for right heart catheterization. The aims of this study were to evaluate the diagnostic ability of echocardiography to detect pulmonary hypertension and increased pulmonary vascular resistance (PVR). METHODS: This retrospective study comprised 118 patients investigated within 48 hours of right heart catheterization. Echocardiography was used to assess pulmonary artery systolic pressure and pulmonary artery mean pressure, filling pressures, cardiac output, and PVR. To diagnose increased PVR, three echocardiographic variables related to pressure reflection in the pulmonary circulation were used. Separate cutoff values aimed at ruling in (high positive likelihood ratio [PLR]) and ruling out (low negative likelihood ratio) pulmonary hypertension (pulmonary artery mean pressure >25 mm Hg) and increased PVR (>3 Wood units) were determined from a derivation group (n = 59, receiver operating characteristic curve analysis) and evaluated in a test group (n = 59). RESULTS: The linear relations between hemodynamic variables assessed with simultaneous echocardiography and right heart catheterization were moderate to strong (R = 0.55 to 0.95), and there were no significant differences, but the limits of agreement were wide. With Doppler pulmonary artery systolic pressure >39 mm Hg, the PLR for pulmonary artery mean pressure >25 mm Hg was 4.7, and with Doppler pulmonary artery systolic pressure ≤29 mm Hg, the negative likelihood ratio was 0.12. The PLR for pressure reflection variables with ruling-in cutoff values ranged from 4.3 to 6.4. With all three variables positive, the PLR was 9.9. The negative likelihood ratio with ruling-out cutoff values ranged from 0.22 to 0.08. CONCLUSIONS: Echocardiography that includes assessment of pressure reflection in the pulmonary circulation can rule in and rule out pulmonary hypertension and increased PVR.

Three decades of heart transplantation in Scandinavia: long-term follow-up.

AIM: Heart transplantation (HTx) has become a standard treatment for patients with end-stage heart disease. The aim of this study was to report the long-term outcome after HTx in Scandinavia. METHODS AND RESULTS: During the period, 1983-2009, 2333 HTxs were performed in 2293 patients (mean age 45 ± 16 years, range 0-70, 78% male). The main indications for HTx were non-ischaemic cardiomyopathy (50%), ischaemic cardiomyopathy (34%), valvular cardiomyopathy (3%), congenital heart disease (7%), retransplantation (2%), and miscellaneous (4%). The registry consists of pre-operative data from recipients and donors, data from pre-operative procedures, and long-term follow-up data. Mean follow-up was 7.8 ± 6.6 years (median 6.9, interquartile range 2.5-12.3, interval 0-27) and no patients were lost to follow-up. Long-term survival for HTx patients was 85, 76, 61, 43, and 30% at 1, 5, 10, 15, and 20 years of follow-up, respectively. Ten-year survival in patients bridged with mechanical circulatory support, in children, after retransplantation, and after concomitant other organ transplantation was 56, 74, 38, and 43%, respectively. Older patients (age > 55 years) had a significantly worse survival (P < 0.001). Patients transplanted more recently had a significantly better survival (P < 0.001). In a multivariate Cox regression analysis, independent predictors of long-term survival were recipient age (P < 0.001), donor age (P < 0.001), diagnosis (P = 0.001), and era of transplantation (P < 0.001). CONCLUSIONS: HTx in Scandinavia proves to have a significantly better survival among patients transplanted in the last decade. HTxs from mechanical circulatory support, in children, after retransplantation, and with concomitant other organ transplantation were performed with acceptable results.

Adaptation and validation of the Cambridge pulmonary hypertension outcome review for Sweden.

BACKGROUND: The Cambridge pulmonary hypertension outcome review (CAMPHOR) is the first pulmonary hypertension-specific instrument for the assessment of the patient's perceived symptoms, activity limitations and quality of life (QoL). PURPOSE: To produce and validate a Swedish language version of the CAMPHOR. METHODS: Bilingual (n = 5) and lay panels (n = 5) were conducted to translate the CAMPHOR into Swedish. This new questionnaire was then field-tested with 14 patients and finally, it underwent psychometric evaluation by means of a postal validation study involving 38 patients with pulmonary hypertension (PH). RESULTS: Few problems were experienced in translating the CAMPHOR into Swedish. The field-test participants found the scales relevant, comprehensible and easy to complete. Psychometric analyses showed that the Swedish adaptation was successful. The Swedish CAMPHOR scales had good internal consistency. Cronbach's alpha coefficients were 0.92 for the symptoms scale, 0.92 for activity limitations and 0.95 for the quality of life. Predicted correlations with the Nottingham Health Profile provided evidence of the construct validity of the scales. The Swedish scales also indicated known groups validity. CONCLUSIONS: The Swedish version of the CAMPHOR is a reliable and valid measure of the impact of pulmonary hypertension on the lives of affected patients. It is recommended for use in clinical studies and routine practice in pulmonary hypertension patients.

Extracorporeal membrane oxygenation as a bridge to lung transplantation in a patient with persistent severe porto-pulmonary arterial hypertension following liver transplantation.

Idiopathic pulmonary artery hypertension (IPAH) is a progressive disease with a dismal prognosis and lung transplantation is often the only option for patients, who do not respond to pharmacological therapy. We report the use of an extracorporeal membrane oxygenation (ECMO) system in a 49-year-old woman with primary pulmonary hypertension, previously liver transplanted. The patient, listed for lung transplantation, developed respiratory and circulatory failure despite maximal pharmacological therapy and was successfully bridged to emergent bilateral lung transplantation with veno-arterial ECMO. Emergent veno-arterial ECMO was able to rescue the patient and bridge her to bilateral lung transplantation and should therefore be an option for patients with PAH and circulatory collapse.

Echocardiography can identify patients with increased pulmonary vascular resistance by assessing pressure reflection in the pulmonary circulation.

BACKGROUND: Pulmonary hypertension is a frequent finding in patients with cardiopulmonary disorders. It is important to recognize pulmonary hypertension due to increased pulmonary vascular resistance (PVR), as this affects treatment and prognosis. Patients with increased PVR have an increased pulmonary pressure reflection. We hypothesized that pressure reflection can be described by echocardiography and that variables related to pressure reflection can identify patients with increased PVR. METHODS AND RESULTS: The study comprised 98 patients investigated within 24 hours of right heart catheterization and 20 control subjects. The pressure reflection variables were obtained by pulsed Doppler in the pulmonary artery and continuous Doppler of tricuspid regurgitation. We selected 3 variables related to pressure reflection: the interval from valve opening to peak velocity in the pulmonary artery (AcT, ms), the interval between pulmonary artery peak velocity and peak tricuspid velocity (tPV-PP, ms), and the right ventricular pressure increase after peak velocity in the pulmonary artery (augmented pressure, AP, mm Hg). The correlation between simultaneous catheter- and echocardiography-determined AP was strong (n=19, R=0.83). The AcT, tPV-PP, and AP in patients with a PVR of >3 Woods units (n=71) was (mean+/-SD) 77+/-16 ms, 119+/-36 ms, and 22+/-12 mm Hg, respectively, and differed from patients with a PVR of

Doppler echocardiography can provide a comprehensive assessment of right ventricular afterload.

BACKGROUND: The purpose of this study was to evaluate novel Doppler echocardiographic methods for a comprehensive assessment of right ventricular afterload, including pulmonary artery (PA) mean pressure (PAMP) and the PA pressure waveform. METHODS: The study comprised 109 patients who underwent right-heart catheterization simultaneously (group A, n = 31) with Doppler echocardiography on 35 occasions or nonsimultaneously (group B, n = 78) within 24 hours of Doppler echocardiography. Right ventricular afterload variables were obtained using pulsed Doppler in the PA and continuous Doppler of tricuspid regurgitation. The intervals from QRS to the opening and closing of the pulmonary valve and to the peak velocity of tricuspid regurgitation were measured. PA end-diastolic pressure, PA systolic pressure, and PA notch pressure were calculated. The Doppler-derived pressure curve was separated into 3 parts with fitted second-order curves. RESULTS: Catheter PAMP and Doppler PA systolic pressure in group A were strongly related (R = 0.85). The regression equation from group A (PAMP = 0.65 x Doppler PA systolic pressure - 1.2 mm Hg) was used to calculate PAMP in group B. There was no difference between catheter PAMP (mean, 39 +/- 18 mm Hg; range, 8-95 mm Hg) and Doppler PAMP (mean, 39 +/- 15 mm Hg; range, 12-83 mm Hg) (P = .85). The systolic areas under the curves for catheter and Doppler PAMP in group A were 20 +/- 4.7 and 20 +/- 4.0 mm Hg s, respectively (P = .52), and the diastolic areas were 21 +/- 5.7 and 22 +/- 6.3 mm Hg s, respectively (P = .21). CONCLUSION: A comprehensive assessment of right ventricular afterload that includes PAMP and the PA pressure waveform can be provided by Doppler echocardiography in patients with a wide range of PA pressures and different diagnoses.

Endothelin-1 across the lung circulation in patients with pulmonary arterial hypertension and influence of epoprostenol infusion.

BACKGROUND: The endothelin-1 (ET-1) system plays a pathophysiologic role in patients with pulmonary arterial hypertension (PAH). Results from previous studies assessing the transpulmonary gradient of ET-1 have been inconsistent. The influence of an intravenous epoprostenol infusion on the transpulmonary ET-1 gradient is unknown. METHODS: In a prospective investigation, serum concentrations of ET-1 were measured in 39 consecutive patients (31 women; mean age, 20-77 years) with pulmonary hypertension (33 with PAH) and compared with 20 controls. The effect of intravenous epoprostenol administration on the transpulmonary gradient of ET-1 was analyzed in 13 patients with pulmonary hypertension. Blood samples were taken simultaneously from the pulmonary artery and radial artery. RESULTS: The serum levels of ET-1 were significantly higher in the arterial (3.9 +/- 1.28 vs 2.53 +/- 0.24 pg/ml, p < 0.001) and mixed venous blood samples (3.9 +/- 1.21 vs 2.52 +/- 0.29 pg/ml, p < 0.001) in patients with pulmonary hypertension than in controls. The arterial/venous ratio of ET-1 in patients (1.0 +/- 0.1) and in the control group (1.0 +/- 0.05) was similar (p = 0.79). During intravenous epoprostenol infusion, there were no changes in the mean transpulmonary ET-1 gradient (0.98 +/- 0.07 vs 0.96 +/- 0.09, p = 0.52), despite significant hemodynamic changes. CONCLUSION: The ET-1 radial artery/pulmonary artery ratio of unity indicates a balanced release and clearance of ET-1 across the lung circulation in controls and in patients with different forms of pulmonary hypertension. ET-1 levels across the pulmonary circulation did not change during epoprostenol infusion.

Pulmonary hemodynamics as predictors of mortality in patients awaiting lung transplantation.

Lung transplantation (LTx) is a therapeutic option for patients with end-stage lung disease. However, the mortality rate of patients on the waiting list is high. The purpose of this study was to examine the prognostic value of cardio-pulmonary hemodynamics for death in patients awaiting LTx. Retrospectively, 177 patients with advanced lung disease accepted for LTx at Sahlgrenska University Hospital from January 1990 through December 2003 were studied. Patient demographics, pulmonary function tests, gas exchange and hemodynamic variables were included in the analysis. Death while awaiting LTx was the primary endpoint for all analyses. Mean age was 49 +/- 9 years. Main diagnoses were alpha 1 antitrypsin deficiency (n = 56), chronic obstructive pulmonary disease (n = 61), cystic fibrosis (n = 14) and interstitial lung disease (n = 46). Thirty patients died (17%). LTx was performed in 143 cases. By univariate analyses, forced vital capacity (FVC) % of predicted, pulmonary vascular resistance (PVR) and diagnosis were associated with risk for death. In multivariate analysis PVR (HR, 1.22; 95% CI, 1.06-1.41; P = 0.006) and FVC% of predicted (HR, 0.97; 95% CI, 0.94-0.99; P = 0.01) were independently associated with death. Patients with increased PVR and a lower FVC % of predicted awaiting LTx should be considered for a higher organ allocation priority. Assessment of pulmonary hemodynamics needs to be considered during evaluation for LTx.