Short-Term Venoarterial Extracorporeal Membrane Oxygenation for Endobronchial Hemorrhage after Pulmonary Endarterectomy

S148

The Journal of Heart and Lung Transplantation, Vol 35, No 4S, April 2016

Purpose: Pulmonary arterial hypertension (PAH) is a progressive and often terminal disease. Inflammatory cytokines and vascular markers may relate to the pathogenesis of PAH and may be biomarkers of disease severity. We sought to investigate biomarker association with clinical parameters at baseline and with outcomes after PAH therapy. Methods: We retrospectively analyzed cytokine and vascular marker data from subjects in the FREEDOM-C2 and TRUST-1 clinical trials of oral and intravenous treprostinil in PAH. Baseline and post-intervention levels of these potential biomarkers were correlated to baseline parameters and also assessed in clinical subgroups based on specified clinical cutoffs and during hospitalizations. Results: 223 patients were included in this study (TRUST= 28, FREEDOM= 195), 194 (TRUST= 16, FREEDOM= 178) had follow-up data at a mean of 15.7 weeks. Among FREEDOM subjects, Ang-2 (R= -0.20, p= 0.006), IL-6 (R= -0.23, p= 0.001), and IL-8 (R= -0.17, p= 0.02) were negatively correlated to 6MWD at baseline. Ang-2 (13.9 vs. 12.2 ng/ml, p= 0.021), IL-6 (5.8 vs. 2.3 ng/ml, P< 0.001) and IL-8 (15.5 vs 11.6 ng/ml, p= 0.015) levels were significantly higher in subjects with 6MWD 360m. Ang-2 (R= 0.67, p< 0.0001), IL-8 (R= 0.30, p= 0.002), and MMP-9 (R= 0.26, p= 0.01) levels were positively correlated to baseline NT-proBNP levels; further, baseline MMP-9 also correlated with a significant decline in NT-proBNP levels in pre vs post-treatment (R= -0.22, p= 0.03). In subjects with NT-proBNP≤ 895 pg/ml, IL-8 (9.1 vs 14.0 ng/ml, p= 0.002) and MMP-9 (86.0 vs 136 ng/ ml, p= 0.035) levels were significantly higher while Ang-2 (7.6 vs 17.3 ng/ ml, p< 0.001) levels were lower. Subjects who were hospitalized had higher baseline IL-8 levels (16.6 vs 13.1 ng/ml, p= 0.004). In the pooled analysis, IL-8 levels remained significantly higher in hospitalized subjects (65.2 vs 13.6 ng/ml, p= 0.012) as were IL-1b (2.6 vs 2.2 ng/ml, p= 0.016) and IL-13 (46 vs. 27.3 ng/ml, p= 0.014). Conclusion: This analysis suggests that Ang-2, IL-8 and MMP-9 are important biomarkers associated with clinical parameters and markers of disease severity in PAH patients including functional capacity, hospitalizations and NT-proBNP levels. 3( 83) Elevated Diastolic Pulmonary Gradient Is Common in the Acute Respiratory Distress Syndrome but Does Not Predict Mortality T. Metkus ,1 E. Tampakakis,1 C. Mullin,1 T. Kolb,1 S. Mathai,1 R. Damico,1 V. Selby,2 T. De Marco,2 P. Hassoun,1 R. Brower,1 R. Tedford.1  1Johns Hopkins Hospital, Baltimore, MD; 2University of California San Francisco, San Francisco, CA. Purpose: Pulmonary vascular dysfunction has been associated with adverse prognosis in acute respiratory distress syndrome (ARDS). The diastolic pulmonary gradient (DPG) has been variably associated with adverse outcomes in pulmonary hypertension (PH) due to left heart disease, however the prevalence of elevated DPG, its determinants, and prognostic value in ARDS is unknown. We hypothesized that elevated DPG would be associated with death. Methods: We performed an analysis of the ARDS Network Fluid and Catheter Treatment Trial of pulmonary artery (PA) catheter use in ARDS, including 392 subjects with a complete hemodynamic data set on trial day 0. DPG was calculated as diastolic PA pressure minus pulmonary artery wedge pressure (PAWP). Cox proportional hazard modeling was performed with primary outcome of death. Results: Mean DPG was 8 ± 6 mmHg on study day 0. Two hundred twentyfour subjects (57.1%) had a DPG ≥  7mmHg, and 183 of these (82%) had concomitant PH (mean PA pressure ≥  25mmHg). The group with elevated DPG had higher PA pressure, pulmonary vascular resistance and airway pressures with lower PAWP (Table). PaO2 was lower in the high DPG group and there was a trend toward worsening acidosis (p= 0.06) and increasing heart rate (p= 0.09). Age, body-surface area, heart rate, PaO2, and pulmonary vascular resistance were predictors of DPG in a multivariate linear regression model. DPG ≥  7 mmHg on day 0 did not predict mortality (HR 1.14 (0.78-1.67); p =  0.5), nor did DPG predict mortality when considered as a continuous variable or at various cutoffs ranging from 3 to 11 mmHg. For 274 subjects with available data on day 0 and day 3, mean DPG did not change significantly over the period (8 ± 5 mmHg on d0 v. 8 ± 5 mmHg on d3, p =  0.55). A DPG greater than 7 mmHg on day 3 did not predict mortality (HR 1.49 [.93-2.4] p =  0.1).

Conclusion: Factors other than pulmonary vascular disease influence DPG in ARDS. In ARDS, an elevated DPG is common but does not predict mortality.

3( 84) Short-Term Venoarterial Extracorporeal Membrane Oxygenation for Endobronchial Hemorrhage after Pulmonary Endarterectomy S. Guth ,1 C.B. Wiedenroth,1 T. Kramm,1 T. Risch,2 M. Wollenschlaeger,3 M.J. Richter,4 H.A. Ghofrani,4 M. Arlt,2 E. Mayer.1  1Department of Thoracic Surgery, Kerckhoff-Clinic, Bad Nauheim, Germany; 2Department of Anesthesiology, Kerckhoff-Clinic, Bad Nauheim, Germany; 3Perfusion Service, Kerckhoff-Clinic, Bad Nauheim, Germany; 4Department of Pulmonology, Kerckhoff-Clinic, Bad Nauheim, Germany. Purpose: Pulmonary endarterectomy (PEA) is the only curative treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH). Massive endobronchial bleeding that precludes weaning from cardiopulmonary bypass is a serious and often fatal complication after PEA. We report 7 consecutive patients with this life-threatening complication that were managed by short-term venoarterial ECMO support. Methods: From January 2014 to October 2015 236 patients (mean age 60.3±16.0 years, female 111, male 125) underwent PEA surgery in our department. In case of severe endobronchial hemorrhage at the time of weaning from extracorporeal circulation patients were directly switched from cardiopulmonary bypass (CPB) to a heparin-coated venoarterial ECMO circuit. After full dose of protamine application to restore normal coagulation weaning from extracorporeal support was attempted in the operating room. Results: Overall in-hospital mortality was 3.0 % (7 / 236 patients). Seven patients (3.0 %; 2 male, 5 female; preoperative PVR 773±340 dynes·s·cm-5) developed severe endobronchial bleeding which was classified as diffuse (n =  5) or localized (n =  2) by bronchoscopy. Following reinstitution of cardiopulmonary bypass and consequent switch to ECMO mean duration of venoarterial ECMO support was 38±17 (20-70) min and all patients could be successfully weaned from the extracorporeal support in the operation theatre without further signs of endobronchial bleeding. One patient needed venovenous ECMO support for poor oxygenation 6 hours after surgery. Finally, six of seven patients after short term venoarterial ECMO support for bronchial hemorrhage could be discharged from the hospital after a prolonged postoperative stay of 17.6±4.1 days. One patient died due to multi-organ failure. Conclusion: For patients with massive endobronchial bleeding after PEA the intraoperative switch from CPB to the venoarterial ECMO support with full-dose protamine administration is a new and potentially life-saving treatment concept.

Abstracts S149 3( 85) Searching for CTEPH; a Swedish National Follow-Up after en Episode of Acute Pulmonary Embolism T. Andersson ,1 B. Carlberg,2 F. Larsen,3 S. Soderberg.1  1Department of Public Health and Clinical Medicine, Cardiology, Umea University, Umea, Sweden; 2Department of Public Health and Clinical Medicine, Medicine, Umea University, Umea, Sweden; 3Department of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden. Purpose: The diagnosis of an acute pulmonary embolism (PE) is associated with difficulties in respect to establishing the diagnosis, treatment options and follow-up. The clinical course is associated with serious co-morbidities such as malignancies and ischaemic heart disease, and is complicated by recurrent episodes of venous thromboembolism, bleeding complications, the development post-thrombotic-syndrome and occasionally a chronic obstruction of the pulmonary vessels that may lead to the development of chronic thromboembolic pulmonary hypertension (CTEPH) a disease associated with high morbidity and mortality. In this study the aim was to follow a one-year national cohort of patients that received the diagnosis of acute pulmonary embolism, to gather information about comorbidities, any remaining symptoms, ECG, lab tests and any investigations done concerning pulmonary hypertension and CTEPH. Methods: In 2005, 5793 patients were found in the Swedish National In-Patient Register with a diagnosis of acute pulmonary embolism. In 2007, 3510 were still alive whereof 13 had already got a diagnosis of CTEPH. These patients were sent a specifically designed questionnaire to find out if they had any remaining symptoms or risk factors for CTEPH. If either risk factors, symptoms and/or elevated NTproBNP levels, the patients and their home clinic got a letter with the request of continuing the follow-up including VQ-scans, echocardiography, and right heart catheterizations when appropriate. Results: The majority of the patients either had remaining dyspnoea or strong risk factors and 1415 of the patients were requested to send blood samples for NTproBNP analysis and an ECG. More than 500 VQ-scans were preformed, about half were considered to be normal and about half had perfusion defects. Another 8 right heart catheterizations were done after echocardiography, and 6 additional patients were diagnosed with CTEPH. Conclusion: In this nation-wide and unique study, nearly half of patients with an episode of acute pulmonary embolism were dead after two years. Many survivors had remaining symptoms of dyspnoea indicating the importance of an appropriate follow-up. Altogether 19 cases with CTEPH were identified found, although many more have symptoms and remaining perfusion defects. 3( 86) Incremental Benefit of Echocardiographic Imaging and Cardiopulmonary Exercise Test in Prognostic Evaluation of Idiopathic Pulmonary Arterial Hypertension R. Badagliacca ,1 S. Papa,1 G. Valli,1 B. Pezzuto,1 R. Poscia,1 G. Manzi,1 E. Giannetta,2 S. Sciomer,1 F. Fedele,1 C.D. Vizza.1  1Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy; 2Experimental Medicine, Sapienza University of Rome, Rome, Italy. Purpose: In idiopathic pulmonary arterial hypertension (IPAH) survival is strongly associated to right ventricle (RV) function. The aim of the study was to evaluate the incremental prognostic value of echocardiographic and cardiopulmonary exercise testing (CPET) on long-term prognosis compared to traditional clinical and hemodynamic parameters. Methods: One hundred-thirty naïve IPAH patients were enrolled in our centre and prospectively followed-up for the presence of clinical worsening (CW). Baseline evaluation included clinical, hemodynamic, echocardiographic and CPET parameters. Cox regression modeling with c-statistic evaluation was realized and internal validation of the Cox analysis based on bootstrapping was considered. Results: During a mean period of 528 ± 304 days, 54 patients presented CW (53%). Among demographic, clinical and hemodynamic parameters, WHO functional class and cardiac index remained independent predictors of CW

(Model-1). Adding echocardiographic and CPET variables (Model-2) peak O2 pulse and RV fractional area change (RVFAC) resulted the only independent factors, significantly improving the power of the prognostic model (AUC: 0.81 vs 0.66, respectively; p= 0.005). Combining together the ROC cut-off values of O2 pulse and RVFAC, patients with high RVFAC/high O2 pulse had significantly a better prognosis compared with the others. Patients with low RVFAC/low O2 pulse and high RVFAC/low O2 pulse showed 99.8 and 29.4 increase in the hazard ratio, respectively, compared with high RVFAC/ high O2 pulse (p= 0.0001). Conclusion: RVFAC and O2 pulse evaluation are able to increase the power of the prognostic model, allowing clinicians to identify at an early stage patients with normal RV systolic function at higher risk of right heart failure before hemodynamic instability appearing. 3( 87) Right Ventricular Dyssynchrony and Exercise Capacity in Idiopathic Pulmonary Arterial Hypertension: Insights Form Echocardiography and Cardiopulmonary Exercise Test R. Badagliacca , R. Poscia, M. Reali, B. Pezzuto, S. Papa, G. Manzi, S. Sciomer, F. Fedele, C.D. Vizza.  Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy. Purpose: In idiopathic pulmonary arterial hypertension (IPAH), characterized by a severe functional limitation due to right heart failure, indices of resting right ventricle (RV) systolic function are not always able to explain the impairment of exercise capacity. Aim of our study was to evaluate if RV dyssynchrony at rest is related to effort tolerance measured by cardiopulmonary exercise test (CPET) and can explain reduced exercise capacity in patients with preserved RV systolic function. Methods: One-hundred and five consecutive stable IPAH patients (majority NYHA class III, severe PH) underwent echocardiographic study and symptom limited CPET. RV dyssynchrony was evaluated by 2D speckle-tracking echocardiography calculating the standard deviation of the times to peaksystolic strain for the 4 mid-basal RV segments (RV-SD4). Patients were grouped by the median value of RV fractional area change (RVFAC, 38%) and compared for RV echocardiographic and CPET parameters. Results: Patients with a RVFAC > 38% presented better morphological and functional echocardiographic parameters and CPET values than the other group. Analyzing the relationship between RVFAC and peak VO2, we found that a significant portion of patient with preserved RVFAC (> 38%) presented low peak VO2. Plotting RV-SD4 and peak VO2, is evident that most of the patients with preserved RVFAC and low peak VO2 show significant RV dyssynchrony. Evaluating the VO2 peak determinants by logistic analysis, model 1, considering only hemodynamic variables, showed cardiac index, right atrial (RA) pressure and pulmonary compliance as the independent predictors, with low predictivity (r2 0.31; p< 0.01). In model 2, considering only echocardiographic variables, and excluding RV dyssynchrony, RVFAC and RA area resulted as independent predictors, with low predictivity comparable to model 1 (r2 0.35; p= < 0.01). Adding dyssynchrony analysis to model 2, RV dyssynchrony significantly improved the power of the predictive model, emerging together with RVFAC and RA area as independent predictor of VO2 peak (r2 0.48; model 3 vs model 1, p< 0.001; model 3 vs model 2, p< 0.001). Conclusion: Our data show that RV dyssynchrony at rest is an independent predictor of peak VO2 and may explain reduced exercise capacity in patients with preserved RV systolic function. 3( 88) Destination Therapy in a Single European Country. Insights from the ITAMACS Registry G. Feltrin ,1 F. Pappalardo,2 G. Gerosa,3 C.F. Russo,4 M. Rinaldi,5 M Maccherini,6 A. Apostolo,7 G. Faggian,8 U. Livi,9 A. Iacovoni,10 M. Massetti,11 F. Musumeci,12 G. Di Giammarco,13 G. Ambrosio,14 A. Loforte,15 D. Pini,16 C. Falletta,17 C. Amarelli,18 A. Grimaldi,19 F.M. Pagani,20 G leonardi,21 A. Frigo,22 L. Rizzato,23 A. Nanni Costa.24  lVeneto Region, Regional Centre for Transplant Coordination, Padova, Italy; 2Cardioth. Department, San Raffaele Hospital, Vita Salute University, Milan, Italy; 3Cardiac, Thoracic, Vascular Sciences, University Hospital of Padova, Padova, Italy; 4Department of Cardiovascular Surgery, A. De Gasperis Cardio Center Niguarda Hospital, Milan, Italy; 5Surgical Sciences, University of Turin, Turin, Italy; 6Cardiothoracic