Search

In patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA) it is important to minimize residual obstructions, in order to achieve low postoperative pulmonary vascular resistances and better clinical results. The aim of the study was to test the hypothesis that the greater the number of pulmonary artery branches treated at surgery, the better the hemodynamic and clinical outcome after PEA. In 564 consecutive CTEPH patients undergoing PEA the count of the number of treated branches was performed directly on the surgical specimens. Post-operative follow-up visits were scheduled at 3 months and 12 months after surgery including right heart catheterization and modified Bruce test. The population was divided into tertiles based on the number of treated branches: Group 1 (from 4 to 30 treated branches, n = 194 patients); Group 2 (from 31 to 43 treated branches, n = 190 patients); Group 3 (from 44 to 100 treated branches, n = 180 patients). At 3 and at 12 months after PEA, after adjustment for confounders, patients in the highest tertile of treated branches had significantly lower values of pulmonary vascular resistance and higher values of pulmonary arterial compliance as compared to the other two groups (p < 0.002). Hospital mortality was 3% in Group 3, 6% in Group 2 and 10% in Group 1 (overall p = 0.035). In CTEPH patients undergoing PEA, a higher number of treated pulmonary artery branches is associated with a better hemodynamic and a better clinical outcome at 3 months and 12 months after surgery. • PEA surgery should be aimed at treating as many distal vessels as possible. • The higher the number of treated vessels the better the hemodynamic outcome. • The higher the number of treated vessels, the better in-hospital and long-term event-free survival • The procedure is safe even in most advances patients. [ABSTRACT FROM AUTHOR]

Introduction: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data.MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup).Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was − 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup.These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged.ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721.Methods: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data.MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup).Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was − 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup.These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged.ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721.Results: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data.MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup).Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was − 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup.These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged.ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721.Conclusion: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data.MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup).Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was − 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup.These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged.ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721.Trial Registration: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data.MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup).Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was − 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup.These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged.ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721. [ABSTRACT FROM AUTHOR]

BACKGROUND: The European Chronic Thromboembolic Pulmonary Hypertension (CTEPH) registry, conducted between 2007 and 2012, reported the major impact of pulmonary endarterectomy (PEA) on the long-term survival of patients with CTEPH. Since then, 2 additional treatments for inoperable CTEPH have become available: balloon pulmonary angioplasty (BPA), and an approved oral drug therapy with the guanylate cyclase stimulator riociguat. The current registry aimed to evaluate the effect of these new therapeutic approaches in a worldwide context. METHODS: Participation in this international global registry included 34 centers in 20 countries. Between February 2015 and September 2016, 1009 newly diagnosed, consecutive patients were included and followed until September 2019. RESULTS: Overall, 605 patients (60%) underwent PEA and 185 (18%) underwent BPA; 76% of the 219 remaining patients not receiving mechanical intervention (ie, neither PEA nor BPA) were treated with pulmonary hypertension drugs. Of patients undergoing PEA and BPA, 38% and 78% also received drugs for pulmonary hypertension, respectively. Median age at diagnosis was higher in the BPA and No PEA/BPA groups than in the PEA group: 66 and 69, respectively, versus 60 years. Pulmonary vascular resistance (PVR) was similar in all groups, with an average of 643 dynes.s.cm−5. During the observation period (>3 years; ≤5.6 years), death was reported in 7%, 11%, and 27% of patients treated by PEA and BPA, and those receiving no mechanical intervention (P <0.001). In Kaplan-Meier analysis, 3-year survival was 94%, 92%, and 71% in the 3 groups, respectively. PEA 3-year survival improved by 5% from that observed between 2007 and 2012. There was no survival difference in patients receiving vitamin K antagonists and non–vitamin K oral anticoagulants (P =0.756). In Cox regression, reduced mortality was associated with: PEA and BPA in the global cohort; history of venous thromboembolism and lower PVR in the PEA group; lower right atrial pressure in the BPA group; and use of pulmonary hypertension drugs, oxygen therapy, and lower right atrial pressure, as well as functional class in the group receiving no mechanical intervention. CONCLUSIONS: This second international CTEPH registry reveals important improvement in patient survival since the introduction of BPA and an approved drug for pulmonary hypertension. The type of anticoagulation regimen did not influence survival. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02656238. [ABSTRACT FROM AUTHOR]

Background In the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase - Stimulator Trial 1 (CHEST-1) study, riociguat improved 6-minute walking distance (6MWD) vs placebo in patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. In this study, the proportion of patients who achieved responder thresholds that correlate with improved outcome in patients with pulmonary arterial hypertension was determined at baseline and at the end of CHEST-1. Methods Patients received placebo or riociguat individually adjusted up to 2.5 mg 3 times a day for 16 weeks. Response criteria were defined as follows: 6MWD increase ≥40 m, 6MWD ≥380 m, cardiac index ≥2.5 liters/min/m 2 , pulmonary vascular resistance <500 dyn∙sec∙cm −5 , mixed venous oxygen saturation ≥65%, World Health Organization functional class I/II, N-terminal pro-brain natriuretic peptide <1,800 pg/ml, and right atrial pressure <8 mm Hg. Results Riociguat increased the proportion of patients with 6MWD ≥380 m, World Health Organization functional class I/II, and pulmonary vascular resistance <500 dyn∙sec∙cm −5 from 37%, 34%, and 25% at baseline to 58%, 57%, and 50% at Week 16, whereas there was little change in placebo-treated patients (6MWD ≥380 m, 43% vs 44%; World Health Organization functional class I/II, 29% vs 38%; pulmonary vascular resistance <500 dyn∙sec∙cm −5 , 27% vs 26%). Similar changes were observed for thresholds for cardiac index, mixed venous oxygen saturation, N-terminal pro-brain natriuretic peptide, and right atrial pressure. Conclusions In this exploratory analysis, riociguat increased the proportion of patients with inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy achieving criteria defining a positive response to therapy. [ABSTRACT FROM AUTHOR]

The article discusses a study that investigated the efficacy and side-effect profile of riociguat in patients with chronic thromboembolic pulmonary hypertension. Data were gathered according to Good Clinical Practice guidelines at the investigation sites. Patients considered to be qualified for trial participation following the first screening were included into a pre-treatment phase. A table outlining baseline demographic and clinical attributes of the patients is presented.

Objectives: Our goal was to investigate the effect of treatment with the oral dual endothelin receptor antagonist bosentan on the hemodynamics and exercise capacity of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Background: CTEPH is characterized by vascular obstruction and remodeling, leading to increased pulmonary vascular resistance (PVR). Although pulmonary endarterectomy (PEA) is potentially curative, medical therapy is needed in patients with inoperable disease or persistent/recurrent pulmonary hypertension after PEA. Methods: The BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension) study was a double-blind, randomized, placebo-controlled study in CTEPH including patients with either inoperable CTEPH or persistent/recurrent pulmonary hypertension after PEA (>6 months after PEA). Independent coprimary end points were change in PVR as a percentage of baseline and change from baseline in 6-min walk distance after 16 weeks of treatment with bosentan or placebo. Secondary end points included change from baseline in World Health Organization functional class and other hemodynamic parameters. Results: One hundred fifty-seven patients were enrolled and randomized: 80 to placebo, 77 to bosentan. A statistically significant treatment effect (TE) of bosentan over placebo on PVR was demonstrated: −24.1% of baseline (95% confidence interval [CI]: −31.5% to −16.0%; p < 0.0001). Total pulmonary resistance (TE: −193 dyn·s·cm−5; 95% CI: −283 to −104 dyn·s·cm−5; p < 0.0001) and cardiac index (TE: 0.3 l·min−1·m−2; 95% CI: 0.14 to 0.46 l·min−1·m−2; p = 0.0007) improved. Mean TE on 6-min walk distance was +2.2 m (95% CI: −22.5 to 26.8 m; p = 0.5449). Bosentan treatment was well tolerated. Conclusions: This study demonstrated a positive TE of bosentan on hemodynamics in this patient population. No improvement was observed in exercise capacity. Further trials are needed to define the role of medical therapy in patients with CTEPH (Bosentan Effects in Inoperable Forms of Chronic Thromboembolic Pulmonary Hypertension; NCT00313222). [Copyright &y& Elsevier]

Abstract: Video-assisted minimally invasive cardiac surgery (VAMICS) is currently performed with various indications. However, despite the increasing evidence of its effectiveness, new approaches have to be defined to simplify this procedure, minimize its potential complications and limit its costs, for a wider use in the surgical community. The limited access to the aorta is a key point in VAMICS and mandates specific clamping modalities with their own limitations, costs and drawbacks. The Portaclamp (Cardio Life Research SA, Louvain la Neuve, Belgium), a new autoguided extravascular aortic cross-clamping system, has been recently proposed to facilitate VAMICS. Herein, we describe the Portaclamp approach and report our indications and preliminary clinical experience so to define its role in VAMICS. [Copyright &y& Elsevier]

Background and objectives: Endothelin-1 (ET-1) and transforming growth factor-β (TGF-β) play a pivotal role in the pathophysiology and vascular remodeling of chronic thromboembolic pulmonary hypertension (CTEPH) which is an under-diagnosed complication of acute pulmonary embolism (PE). Currently, pulmonary endarterectomy (PEA) is still the treatment of choice for selected patients suffering from CTEPH. The aim of this study was to evaluate the preoperative and postoperative circulating levels of ET-1 and TGF-β in subjects affected by CTEPH undergoing successful surgical treatment by PEA. Methods: The data from patients diagnosed with CTEPH who underwent PEA at the Foundation IRCCS Policlinico San Matteo Hospital (Pavia, Italy) were prospectively recorded in the Institutional database. Circulating ET-1 and TGF-β levels were assessed by an ELISA commercial kit before PEA, at 3 months and 1 year after PEA. The demographic data, preoperatory mean pulmonary arterial pressure (mPAP), cardiac output (CO), and pulmonary vascular resistance (PVR) were also recorded. Univariate and multivariate analyses were performed. Results: The analysis included 340 patients with complete ET-1 measurements and 206 patients with complete TGF-β measurements. ET-1 significantly decreased both at 3 months (p < 0.001) and at 1 year (p = 0.009) after PEA. On the other hand, preoperatory TGF-β levels did not significantly change after PEA. Furthermore, ET-1, but not TGF-β, was a good predictor for increased mPAP in multivariate analyses (p < 0.05). Conclusions: ET-1 but not TGF β was significantly modulated by PEA in subjects affected by CTEPH up to 1 year after surgery. The mechanisms leading to prolonged elevated circulating TGF-β levels and their clinical significance have to be further elucidated. [ABSTRACT FROM AUTHOR]

Background: After successful pulmonary endoarterectomy (PEA), patients may still suffer from exercise limitation, despite normal pulmonary vascular resistance. We sought to assess the proportion of these patients after the extension of PEA to frail patients, and the determinants of exercise limitation.Methods: Out of 553 patients treated with PEA from 2008 to 2016 at our institution, a cohort of 261 patients was followed up at 12 months. They underwent clinical, haemodynamic, echocardiographic, respiratory function tests and treadmill exercise testing. A reduced exercise capacity was defined as Bruce test distance < 400 m.Results: Eighty patients did not had exercise testing because of inability to walk on treadmill and/or ECG abnormalities Exercise limitation 12 months after PEA was present in 74/181 patients (41, 95%CI 34 to 48%). The presence of COPD was more than double in patients with exercise limitation than in the others. Patients with persistent exercise limitation had significantly higher mPAP, PVR, HR and significantly lower RVEF, PCa, CI, VC, TLC, FEV1, FEV1/VC, DLCO, HbSaO2 than patients without. The multivariable model shows that PCa at rest and TAPSE are important predictors of exercise capacity. Age, COPD, respiratory function parameters and unilateral surgery were also retained.Conclusions: After successful PEA, most of the patients recovered good exercise tolerance. However, about 40% continues to suffer from limitation to a moderate intensity exercise. Besides parameters of right ventricular function, useful information are provided by respiratory function parameters and COPD diagnosis. This could be useful to better address the appropriate therapeutic approach. [ABSTRACT FROM AUTHOR]

To verify whether the new hemodynamic definition of pulmonary hypertension (PH) has any implication in treatment of Chronic Thrombo-Embolic Pulmonary Disease (CTEPD) patients without PH, we retrospectively analysed the clinical and functional changes determined by pulmonary endarterectomy (PEA) in 63 CTEPD patients without PH who underwent surgery at our center, comparing those in whom the hemodynamic diagnosis of PH met recent guideline recommendations versus those in whom the diagnosis only met previous hemodynamic thresholds. The results show that the vast majority of CTEPD patients without PH operated at our center would now be defined as chronic thromboembolic pulmonary hypertension (CTEPH) patients. PEA did not result in any improvement in exercise capacity nor in right ventricular function or lung function test in patients with mean pulmonary artery pressure (mPAP) ≤ 20 mm Hg and pulmonary vascular resistance (PVR) ≤ 2 WU; on the contrary, hemodynamic parameters, exercise capacity, right ventricular function and lung function significantly improved in patients with mPAP between 21 and 24 mm Hg. [ABSTRACT FROM AUTHOR]

Abstract: We present postoperative and midterm (3 years) angiographic changes after removal of five (of six) occluded stents from the left anterior descending (LAD) coronary artery and its reconstruction with a 9-cm-long on-lay patching done with the left internal mammary artery. [Copyright &y& Elsevier]

Pulmonary veno‐occlusive disease (PVOD) is a rare disease. It may be idiopathic or associated, in particular, with connective tissue disease, or it may develop after radiation exposure; in heritable forms of PVOD, the inheritance is autosomal recessive due to the presence of homozygous or compound heterozygous pathogenic variants in the EIF2AK4 gene. We describe the case of a young man whose PVOD was initially misdiagnosed as chronic thromboembolic pulmonary hypertension despite worsening after riociguat, nonspecific computed tomography pulmonary angiogram findings, and parental consanguinity could suggest an autosomal recessive disease. The correct diagnosis and the correct treatment are crucial given the high mortality rate of this disease. [ABSTRACT FROM AUTHOR]

The author presents information on fibrinogen. Fibrinogen, or coagulation factor I, is a main player in thrombus formation. It is split by thrombin to form fibrin, which is the most abundant component of a blood clot. It is a proinflammatory factor in autoimmune and inflammatory diseases, such as rheumatoid arthritis, vasculitides, inflammatory bowel disease and multiple sclerosis.

ISHLT members have recognized the importance of a consensus statement on the evaluation and management of patients with chronic thromboembolic pulmonary hypertension. The creation of this document required multiple steps, including the engagement of the ISHLT councils, approval by the Standards and Guidelines Committee, identification and selection of experts in the field, and the development of 6 working groups. Each working group provided a separate section based on an extensive literature search. These sections were then coalesced into a single document that was circulated to all members of the working groups. Key points were summarized at the end of each section. Due to the limited number of comparative trials in this field, the document was written as a literature review with expert opinion rather than based on level of evidence. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to describe the radiological features of chronic thromboembolic pulmonary disease (CTEPD), not yet systematically described in the literature. Furthermore, we compared vascular scores between CTEPD and chronic thromboembolic pulmonary hypertension (CTEPH) patients, trying to explain why pulmonary hypertension does not develop at rest in CTEPD patients. Methods: Eighty-five patients (40 CTEPD, 45 CTEPH) referred to our centre for pulmonary endarterectomy underwent dual-energy computed tomography pulmonary angiography (DE-CTPA) with iodine perfusion maps; other 6 CTEPD patients underwent single-source CTPA. CT scans were reviewed independently by an experienced cardiothoracic radiologist and a radiology resident to evaluate scores of vascular obstruction, hypoperfusion and mosaic attenuation, signs of pulmonary hypertension and other CT features typical of CTEPH. Results: Vascular obstruction burden was similar in the two groups (p = 0.073), but CTEPD patients have a smaller extension of perfusion defects in the iodine map (p = 0.009) and a smaller number of these patients had mosaic attenuation (p < 0.001) than CTEPH patients, suggesting the absence of microvascular disease. Furthermore, as expected, the two groups were significantly different considering the indirect signs of pulmonary hypertension (p < 0.001). Conclusions: CTEPD and CTEPH patients have significantly different radiological characteristics, in terms of signs of pulmonary hypertension, mosaic attenuation and iodine map perfusion extension. Importantly, our results suggest that the absence of peripheral microvascular disease, even in presence of an important thrombotic burden, might be the reason for the absence of pulmonary hypertension in CTEPD. Key Points: • CTEPD and CTEPH patients have significantly different radiological characteristics. • The absence of peripheral microvascular disease might be the reason for the absence of pulmonary hypertension in CTEPD. [ABSTRACT FROM AUTHOR]

Few studies addressed the issue of risk stratification in patients with residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). This study tested the potential added value of parameters that have not been included in existing risk models. We evaluated 546 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent PEA and were followed-up for a median period of 58 months. Among the 242 with residual PH, 27 died and had 127 a clinical worsening event. At univariable analysis, the parameters associated with poor survival were pulmonary vascular resistance (PVR) ≥425 dyn·s·cm−5 (p ≤ 0.001), mean pulmonary artery pressure (mPAP) ≥38 mmHg (p = 0.003) and pulmonary artery compliance (CPA) ≤1.8 ml/mmHg (p = 0.014). In the bivariable models including either PVR or mPAP as first parameter, the addition of CPA was not statistically significant. The parameters associated with poor clinical worsening were CPA ≤1.8 ml/mmHg (p < 0.001), PVR ≥425 dyn·s·cm−5 (p = 0.002), arterial oxygen tension (PaO2) ≤ 75 mmHg (p = 0.003), mPAP ≥38 mmHg (p = 0.008). In a multivariable analysis which included PVR ≥425 as the first parameter, the addition of both CPA ≤1.8 ml/mmHg and of PaO2 ≤ 75 mmHg significantly improved prognostic stratification (Harrel's C of the model = 0.64, p < 0.001). Noticeably, the lower tertile of the model's predictor index identified a subgroup of 91 patients who had an event rate numerically similar to that of patients without residual PH. Risk stratification in residual PH can be refined if CPA and PaO2 are considered in association with standard hemodynamic parameters. • Few studies address the issue of risk stratification in patients with residual pulmonary hypertension after pulmonary endarterectomy • Risk stratification can be refined if pulmonary arterial compliance and arterial oxygen tension are considered with hemodynamic parameters. • It is thus possible to identify a subgroup of patients who have an event rate similar to that of patients without residual pulmonary hypertension. • Risk stratification can be used to guide therapy in such patients. [ABSTRACT FROM AUTHOR]

There is little evidence on the long-term effects of calcineurin inhibitor (CNI) withdrawal and substitution with everolimus and mycophenolate mofetil in maintenance therapy of patients who have received heart transplants and have concurrent CNI nephrotoxicity. Aims of this study were to evaluate the progression of renal dysfunction after discontinuation of CNIs and to monitor for major adverse events after therapy change. Data from 41 patients who underwent heart transplant and have different degrees of renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2), without evidence of proteinuria, and in whom CNI therapy was replaced by everolimus, were analyzed. At the time of CNI withdrawal, clinical parameters, echocardiographic data, blood tests of renal function, and monitoring of adverse events were recorded. The median follow-up period was 5 years ± 28 months. In 52% of patients, there was a clear improvement in renal function (10.5 mL/min/1.73 m2 of extra eGFR on average). The former were characterized by less advanced age and a short time from the heart transplant. The echocardiographic parameters showed a significant reduction in septum thickness (11.58 ± 2 mm vs 10.29 ± 2 mm; P =.0001) and in left ventricle posterior wall thickness (10.74 ± 1 mm vs 9.74 ± 1 mm; P =.0004). The incidence of late acute rejection and cardiac allograft vasculopathy was similar in our population compared to literature data. A therapeutic switch from CNIs to everolimus and mycophenolate mofetil can improve renal function in patients with CNI nephrotoxicity, especially in those with a shorter time period from transplantation, without exposing them to a higher incidence of late acute rejection and cardiac allograft vasculopathy. • Replacement of calcineurin inhibitor (CNI) immunosuppressive maintenance regimens with everolimus plus mycophenolate can reduce deterioration of renal function induced by CNIs. • CNI withdrawal in selected patients years after transplantation seems to be safe in terms of late acute rejection and could protect against cardiac allograft vasculopathy. • An everolimus plus mycophenolate immunosuppressive regimen could be effective in reducing negative cardiac remodeling, probably due to different factors. [ABSTRACT FROM AUTHOR]

Background: After undergoing a procedure of pulmonary endarterectomy (PEA), patients with chronic thromboembolic pulmonary hypertension (CTEPH) may still experience reduced exercise capacity. Data on effects of exercise training in these patients are scant. Objectives: To evaluate the effectiveness of exercise training after PEA for CTEPH and if the presence of "residual pulmonary hypertension" may affect the outcome. Methods: Retrospective data analysis of CTEPH patients undergoing inpatient exercise training after PEA. According to predefined criteria, patients were divided into those with (group 1) and without (group 2) a "good" post-surgery hemodynamic response. Assessments of the 6-min walking distance test (6-min walking distance test [6 MWT]: primary outcome) were performed before and after surgery (before training), after training and at 3-month follow-up. Hemodynamic and lung function data were also analyzed. Results: Data of 84 and 26 patients of groups 1 and 2, respectively, were analyzed. After surgery patients showed a reduction in 6 MWT, which significantly reversed after training and further improved at 3 months (p = 0.0001), without any significant difference between groups. The percentage of patients reaching the minimal clinically important difference in 6 MWT was similar between groups. The sig - nificant (p = 0.0001) post-surgery improvement in hemodynamics was maintained at 3 months without any significant difference between groups. New York Heart Association functional class improved in parallel to the hemodynamic improvement. Conclusions: Exercise training in patients with CTEPH after PEA, an inpatient exercise training program, improves exercise capacity for up to 3 months, independently of the post-surgery hemodynamic response. [ABSTRACT FROM AUTHOR]

Acute pulmonary embolism (APE) is a well-described complication following surgical procedures. The incidence of such a complication can be related to the presence of a peculiar patient's condition. Cryoglobulinemia, which consists in the presence of one or more immunoglobulins in the serum that precipitate at temperatures below 37°C and redissolve on warming, seems to increase the risk of thrombotic events. Treatment options of APE, according to clinical severity, include systemic thrombolysis, surgical embolectomy, and systemic anticoagulation. Thrombolysis is considered the first-line treatment, whereas surgery is reserved in case of extremely-compromised hemodynamic conditions related to massive central embolism, and in case of contraindication to thrombolysis. Here, we report a case of acute massive pulmonary embolism occurring at the end of a surgical procedure for a thymic carcinoma resection, in a patient with cryoglobulinemia, which required an emergent surgical pulmonary embolectomy. [ABSTRACT FROM AUTHOR]

Background It has been hypothesized that pre-capillary pulmonary hypertension (PH) may trigger sleep disordered breathing (SDB). In patients with chronic thromboembolic PH (CTEPH), pulmonary endarterectomy (PEA) is potentially effective to improve PH. We assessed the pre- and post-operative prevalence of SDB in CTEPH patients submitted to PEA and the relationship between SDB and clinical, pulmonary and hemodynamic factors. Methods Unattended cardiorespiratory recording was performed the night before and one month after elective PEA in 50 patients. Results Before the intervention SDB prevalence (obstructive or central AHI ≥ 5/h) was 64%: 18 patients (66% female) had No-SDB, 22 (68% female) had dominant obstructive (dOSA), and 10 (20% female) had dominant central sleep apnea (dCSA). There were no differences in risk factors and the need for supplemental oxygen. Mean right atrial (mRAP) and pulmonary artery pressures (mPAP) showed a more compromised profile from No-SDB to dOSA and dCSA (mRAP: 5.5 ± 3.9 vs 7.0 ± 4.5 vs 9.7 ± 4.3 mm Hg (p = 0.054), mPAP: 39 ± 12 vs 48 ± 11 vs 51 ± 16 mm Hg (p = 0.0.47)). By contrast, cardiac index did not differ. At post-intervention, the prevalence of SDB was 68%: 16 patients had No-SDB, while 30 had dOSA and 4 dCSA, with no relationship with the relief from PH. Interestingly, 5 patients with previous CSA moved to the OSA group and 2 normalized. Conclusions Prevalence of SDB is high in patients with CTEPH even after resolution of PH. Our data support the hypothesis that pre-capillary PH may trigger CSA but not OSA, and suggest that OSA may play a role in the development of CTEPH. [ABSTRACT FROM AUTHOR]

Background In this prospective, single-center, observational study, we investigated the association between repeated short periods of circulatory arrest with moderate hypothermia during pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and different neuropsychological dimensions. Methods We examined 70 patients with CTEPH, >18 to 80 years of age, who had been treated with PEA. Neuropsychological testing was performed. Results Learning ability and delayed memory remained well within the normal range for patients’ age. We found a statistically significant post-surgical improvement in motor speed, which was accompanied by a better quality of life and reduced symptoms of depression and anxiety. Conclusion PEA with repeated short periods of circulatory arrest in CTEPH did not result in any neuropsychological complications and may even lead to post-surgical psychological improvements. [ABSTRACT FROM AUTHOR]

Abstract: Axillary artery has been proposed as a safe and effective alternative for arterial cannulation in surgical procedures involving ascending aorta and/or aortic arch, and is nowadays the site of choice in many centres. Advantages of axillary artery cannulation include antegrade flow and the possibility of selective mono-hemispherical brain perfusion during circulatory arrest. Experiences with the axillary vein cannulation, however, are scarce. Here we report our preliminary experience with axillo-axillary cardiopulmonary bypass, through both axillary artery and vein cannulation (using echo-guided Seldinger technique) at deltoido-pectoralis groove. We have used such an approach in 5 cases of redo surgery on ascending aorta and we have not had any inconvenience during cardiopulmonary bypass. Full flow was maintained in all patients (in 2 with vacuum assisted drainage) including 2 cases with deep hypothermic circulatory arrest. In conclusion such an approach seems to be feasible and effective and can be safely performed providing that accurate TE echo monitoring is provided. [Copyright &y& Elsevier]

Background: Chronic thromboembolic pulmonary hypertension, a rare complication of acute pulmonary embolism, is characterized by fibrothrombotic obstructions of large pulmonary arteries combined with small-vessel arteriopathy. It can be cured by pulmonary endarterectomy, and can be clinically improved by medical therapy in inoperable patients. A European registry was set up in 27 centers to evaluate long-term outcome and outcome correlates in 2 distinct populations of operated and not-operated patients who have chronic thromboembolic pulmonary hypertension.Methods and Results: A total of 679 patients newly diagnosed with chronic thromboembolic pulmonary hypertension were prospectively included over a 24-month period. Estimated survival at 1, 2, and 3 years was 93% (95% confidence interval [CI], 90-95), 91% (95% CI, 87-93), and 89% (95% CI, 86-92) in operated patients (n=404), and only 88% (95% CI, 83-91), 79% (95% CI, 74-83), and 70% (95% CI, 64-76) in not-operated patients (n=275). In both operated and not-operated patients, pulmonary arterial hypertension-targeted therapy did not affect survival estimates significantly. Mortality was associated with New York Heart Association functional class IV (hazard ratio [HR], 4.16; 95% CI, 1.49-11.62; P=0.0065 and HR, 4.76; 95% CI, 1.76-12.88; P=0.0021), increased right atrial pressure (HR, 1.34; 95% CI, 0.95-1.90; P=0.0992 and HR, 1.50; 95% CI, 1.20-1.88; P=0.0004), and a history of cancer (HR, 3.02; 95% CI, 1.36-6.69; P=0.0065 and HR, 2.15; 95% CI, 1.18-3.94; P=0.0129) in operated and not-operated patients, respectively. Additional correlates of mortality were bridging therapy with pulmonary arterial hypertension-targeted drugs, postoperative pulmonary hypertension, surgical complications, and additional cardiac procedures in operated patients, and comorbidities such as coronary disease, left heart failure, and chronic obstructive pulmonary disease in not-operated patients.Conclusions: The long-term prognosis of operated patients currently is excellent and better than the outcome of not-operated patients. [ABSTRACT FROM AUTHOR]

• Patient-specific approach to estimate pulmonary artery stiffness based on MRI images. • Maximum likelihood estimation approach that exploits a full vessel constitutive law. • Young's modulus derived in terms of mean value and standard deviation. • Entire boundary and an arc free from surrounding structures separately considered. • Approach applied to pulmonary endarterectomy for treating thromboembolic hypertension. An accurate non-invasive evaluation of the mechanical properties of the vessel wall is important for a variety of screening protocols and surgical treatments. In this work, we focused on a section of the Pulmonary Artery (PA), and developed a patient-specific approach to estimate its stiffness in terms of the Young's modulus along the circumferential direction (E). First, we developed a patient-specific semi-automatic approach to estimate its expected value and standard deviation. To this end, pressure-length curves were derived from magnetic resonance images acquired during the cardiac cycle and information on vessel pressure obtained by catheterization. Then, the estimates of E were derived through a maximum likelihood estimation approach based on a vessel constitutive law. In particular, we analyzed the entire PA boundary and an arc free from surrounding organs. Second, we applied the approach to the study of pulmonary endarterectomy (PEA) for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). We observed a decrease in the circumferential E after PEA for the whole boundary, while no clear trend was observed for the free arc. The low standard deviations associated with the estimates showed high accuracy when considering the entire boundary, while greater variability was observed for the free arc, which was however limited. Finally, reliable hysteretic behavior was obtained from the reconstructed pressure-length curves. [ABSTRACT FROM AUTHOR]

Background: Heart involvement is the leading cause of death of patients with eosinophilic granulomatosis with polyangiitis (EGPA; formerly Churg-Strauss syndrome) and is more frequent in anti-neutrophil cytoplasm antibody (ANCA)-negative patients. Post-transplant outcome has only been reported once. Methods: We conducted a retrospective international multicenter study. Patients satisfying the criteria of the American College of Rheumatology and/or revised Chapel Hill Consensus Conference Nomenclature were identified by collaborating vasculitis and transplant specialists, and the help of the Churg-Strauss Syndrome Association. Results: Nine ANCA- patients who received transplants between October 1987 and December 2009 were identified. The vasculitis and cardiomyopathy diagnoses were concomitant for 5 patients and separated by 12 to 288 months for the remaining 4 patients. Despite ongoing immunosuppression, histologic examination of 7 (78%) patients' explanted hearts showed histologic patterns suggestive of active vasculitis. The overall 5-year survival rate was low (57%), but rose to 80% when considering only the 6 patients transplanted during the last decade. After survival lasting 3 to 60 months, 4 (44%) patients died sudden deaths. Conclusions: The search for EGPA-related cardiomyopathy is mandatory early in the course of this type of vasculitis. Indeed, prompt treatment with corticosteroids and cyclophosphamide may achieve restore cardiac function. Most patients in this series were undertreated. For patients with refractory EGPA, heart transplantation should be performed, which carries a fair prognosis. No optimal immunosuppressive strategy has yet been identified. [ABSTRACT FROM AUTHOR]

The article presents a retrospective study aimed at analyzing functional recovery and response to rehabilitation treatment in immediate postoperative phase of aortocoronary bypass (ACB) surgery, which described a protocol of early rehabilitative treatment for functional recovery after the surgery.

Abstract: Transfusions in cardiac surgery are associated with an increased morbidity and mortality rate. However, no information is available with respect to the recovery process of transfused patients after discharge from the hospital. Two-hundred-seventeen patients who underwent cardiac surgery operations requiring packed red cells transfusions were studied during the rehabilitation stay. The exercise tolerance (6-min walk test) was not dependent on the number of packed red cells units transfused. Conversely, the length of stay in the rehabilitation hospital was independently associated (P =0.004) with the number of packed red cells transfused, with an increase of 0.6days per each unit transfused. [Copyright &y& Elsevier]

Background: Elevated heart rate (HR) has been indicated as risk factor for cardiovascular disease. Experimental data support a role of HR in the progression and severity of atherosclerotic lesions. Sinus tachycardia is common in heart transplant patients due to the lack of autonomic control. This study assessed the role of HR in the development of cardiac allograft vasculopathy (CAV) in heart transplant recipients. Methods: Data from 244 allograft recipients were analyzed. Known factors affecting CAV and mean HR obtained from 24-hour recordings at 1 year (dichotomized at ≥90 beats/min) were tested in univariate and multivariable Cox analysis. Results: During a median of 96 months, 60 patients (25%) experienced CAV. Surprisingly, HR < 90 but not ≥90 beats/min was significantly associated with an increased CAV development. Univariate analysis showed several predictors were associated with the end point; however, at multivariable analysis, only donor''s age, chronic renal failure, and left ventricular end-diastolic wall thickness were significant predictors of CAV, with hazard ratios of 1.02 (95% confidence interval, 1.00–1.04), 1.90 (1.13–3.21), and 1.11 (1.00–1.22), respectively. A highly statistically significant difference in donor''s age was found among patients with mean heart rate ≥90 or <90 beats/min (30 ± 13 vs 40 ± 14 years, p < 0.0001). Conclusions: In the denervated heart, sinus tachycardia is not a risk factor for coronary atherosclerosis. HR in heart transplant recipients reflects “intrinsic heart rate” and is a simple epiphenomenon of the donor''s age. [ABSTRACT FROM AUTHOR]

Background--Chronic thromboembolic pulmonary hypertension (CTEPH) is often a sequel of venous thromboembolism with fatal natural history; however, many cases can be cured by pulmonary endarterectomy. The clinical characteristics and current management of patients enrolled in an international CTEPH registry was investigated. Methods and Results--The international registry included 679 newly diagnosed (≤6 months) consecutive patients with CTEPH, from February 2007 until January 2009. Diagnosis was confirmed by right heart catheterization, ventilation-perfusion lung scintigraphy, computerized tomography, and/or pulmonary angiography. At diagnosis, a median of 14.1 months had passed since first symptoms; 427 patients (62.9%) were considered operable, 247 (36.4%) nonoperable, and 5 (0.7%) had no operability data; 386 patients (56.8%, ranging from 12.0%-60.9% across countries) underwent surgery. Operable patients did not differ from nonoperable patients relative to symptoms, New York Heart Association class, and hemodynamics. A history of acute pulmonary embolism was reported for 74.8% of patients (77.5% operable, 70.0% nonoperable). Associated conditions included thrombophilic disorder in 31.9% (37.1% operable, 23.5% nonoperable) and splenectomy in 3.4% of patients (1.9% operable, 5.7% nonoperable). At the time of CTEPH diagnosis, 37.7% of patients initiated at least 1 pulmonary arterial hypertension-targeted therapy (28.3% operable, 53.8% nonoperable). Pulmonary endarterectomy was performed with a 4.7% documented mortality rate. Conclusions--Despite similarities in clinical presentation, operable and nonoperable CTEPH patients may have distinct associated medical conditions. Operability rates vary considerably across countries, and a substantial number of patients (operable and nonoperable) receive off-label pulmonary arterial hypertension-targeted treatments. [ABSTRACT FROM AUTHOR]

The aim of the present study was to assess the clinical and prognostic significance of right ventricular (RV) dilation and RV hypertrophy at echocardiography in patients with idiopathic pulmonary arterial hypertension. Echocardiography and right heart catheterization were performed in 72 consecutive patients with idiopathic pulmonary arterial hypertension admitted to our institution. The median follow-up period was 38 months. The patients were grouped according to the median value of RV wall thickness (6.6 mm) and the median value of the RV diameter (36.5 mm). On multivariate analysis, the mean pulmonary artery pressure (p = 0.018) was the only independent predictor of RV wall thickness, and age (p = 0.011) and moderate to severe tricuspid regurgitation (p = 0.027) were the independent predictors of RV diameter. During follow-up, 22 patients died. The death rate was greater in the patients with a RV diameter >36.5 mm than in patients with a RV diameter ≤36.5 mm: 15.9 (95% confidence interval 9.4 to 26.8) vs 6.6 (95% confidence interval 3.3 to 13.2) events per 100-person years (p = 0.0442). In contrast, the death rate was similar in patients with RV wall thickness above or below the median value. However, among the patients with a RV wall thickness >6.6 mm, a RV diameter >36 mm was not associated with a poorer prognosis (p = 0.6837). In conclusion, in patients with idiopathic pulmonary arterial hypertension, a larger RV diameter is a marker of a poor prognosis but a greater RV wall thickness reduces the risk of death associated with a dilated right ventricle. [ABSTRACT FROM AUTHOR]

Abstract: Background: In patients with idiopathic pulmonary hypertension (IPAH) progression of the disease and survival are related to the capability of the right ventricle to adapt to the chronically elevated pulmonary artery pressure. Although several echocardiographic variables have been associated with outcome in previous studies, a comparative evaluation of all right ventricular (RV) function indices obtainable at echocardiography has never been performed. Methods: 59 patients consecutively admitted in a tertiary referral centre because of IPAH (22 males, mean age 46.3±16.1 years, 68% in WHO class III/IV at referral) underwent right heart catheterization and echocardiography. During a median follow-up period of 52 months, 21 patients died and 2 underwent lung transplantation in emergency conditions. Results: The following parameters were associated with survival: tricuspid annular plane systolic excursion (TAPSE), RV fractional area change, degree of tricuspid regurgitation, inferior vena cava collapsibility, superior vena cava flow velocity pattern, left ventricular diastolic eccentricity index. Patients with TAPSE≤15 mm and left ventricular eccentricity index ≥1.7 had the highest event rate (51.7 per 100 person year); patients with TAPSE>15 mm and mild or no tricuspid regurgitation had the lowest event rate (2.6 per 100 person year). Conclusions: A comprehensive echocardiographic assessment of RV systolic and diastolic function based on TAPSE, left ventricular diastolic eccentricity index and degree of tricuspid regurgitation allows an accurate prognostic stratification of patients with IPAH. [Copyright &y& Elsevier]

Abstract: Background: Re-do mitral valve procedures performed through median sternotomy carry substantial mortality and morbidity. To avoid complications of sternal re-entry and to provide adequate mitral valve exposure, antero-lateral thoracotomy has been suggested by some authors. Methods: From October 1997 to January 2007, 677 mitral valve operations have been performed in our centre using port-access video-assisted right mini-thoracotomy. Among these, 241 (35.6%) were performed on patients who had undergone one or more previous cardiac surgery procedures. Results: Mean cardio-pulmonary bypass time and endo-clamp time were 117±46min and 71±31min, respectively. Arterial cannulation was performed either on the ascending aorta, with the endo-direct cannula (112 patients, 46.5%), or peripherally with a femoral artery approach (129 patients, 53.5%). Conversion to median sternotomy was necessary in only two patients (0.8%) due to aortic dissection (one case) and left ventricle free wall rupture (one case). Median intensive care unit stay was 24h, median mechanical ventilation time was 12h; median hospital stay was 8 days. Bleeding requiring surgical revision occurred in 12 patients (4.9%). Hospital mortality was 4.9% (12/241 patients). Conclusions: Port-access video-assisted right mini-thoracotomy allows good results in a difficult subset of patients; it allows minimal adhesion dissection, short ICU and hospital stay. In our practice, this technique has become the treatment of choice for mitral valve re-do surgery. [Copyright &y& Elsevier]

Cardiac retransplantation represents the gold standard treatment for a failing cardiac graft but the decision to offer the patient a second chance is often made difficult by both lack of donors and the ethical issues involved. The aim of this study was to evaluate whether retransplantation is a reasonable option in case of early graft failure. Between November 1985 and June 2008, 922 patients underwent cardiac transplantation at our Institution. Of these, 37 patients (4%) underwent cardiac retransplantation for cardiac failure resulting from early graft failure ( n = 11) or late graft failure (acute rejection: n = 2, transplant-related coronary artery disease: n = 24). Survival at 1, 5 and 10 years of patients with retransplantation was 59%, 50% and 40% respectively. An interval between the first and the second transplantation of less than ( n = 11, all in early graft failure) or more than ( n = 26) 1 month was associated with a 1-year survival of 27% and 73%, and a 5-year survival of 27% and 65% respectively ( P = 0.01). The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation only in patients with transplant-related coronary artery disease. Early graft failure is a significant risk factor for survival after cardiac retransplantation and should be considered as an exclusion criteria. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the rate of return to work after transplantation and its determinants in a clinically-stable population of patients transplanted and followed-up at a single institution in Italy. Methods: 151 thoracic organ transplant recipients (72 lung, 79 heart) were examined. Patients were asked about daily activities, level of education, employment and clinical condition. A six-minute walking test was performed with measurement of dyspnoea using the Borg scale. Quality of Life was evaluated with the SF-36 and GHQ questionnaires. Results: Before transplantation 131 patients (87%), (70 heart and 61 lung) worked. After transplantation, 51 patients (39%) went back to work and 3 more started working. We found that younger age, a better quality of life (mainly in the mental domain), having had an occupation previously (particularly as an entrepreneur/freelancer), and having been off work for less than 24 months, were independent predictors of return to work. Conclusions: Considering their good, objective and subjective, functional status, some patients who could have returned to work, chose not to. Identifying factors which affect return to work might help health professionals to adopt the best course of treatment and psychological support in order to fulfil this goal; however, return to work should not be considered as the only expression of a patient''s real psychophysical condition. [Copyright &y& Elsevier]

Background: Bronchiolitis obliterans syndrome is the main long-term complication of lung transplantation that limits survival of lung transplant patients. Its pathophysiologic mechanisms are still poorly understood but it seems to result from a chronic immunologic/inflammatory insult leading to excessive fibroproliferation. The aim of this longitudinal study of 44 lung recipients was to determine whether a number of bronchoalveolar lavage and clinical variables are associated with a higher risk of developing bronchiolitis obliterans syndrome.Methods: Bronchoalveolar lavage studies involved assessment of several cytokines including: interleukin-8, monocyte chemoattractant protein-1, regulated-upon-activation normal T cell expressed and secreted (RANTES), gamma-interferon, interleukin-12, interleukin-10 and transforming growth factor-beta.Results: The predictivity of bronchoalveolar lavage (BAL) features with respect to onset of bronchiolitis obliterans syndrome was assessed by the Cox regression model. Among clinical variables, bacterial and viral infections were found to significantly predict occurrence of bronchiolitis obliterans syndrome (hazard ratio [HR] for bacterial infection: 13.044, 95% confidence interval [CI] 1.34 to 126.69, p = 0.027; HR for viral infections: 4.88, 95% CI 1.004 to 22.87, p = 0.05). Among BAL variables, only IL-12 was significantly predictive of bronchiolitis obliterans syndrome (HR 0.956, 95% CI 0.901 to 1.01, p = 0.03). In addition, in a sub-group cross-sectional analysis, bronchiolitis obliterans syndrome patients were compared with clinically stable patients, and significant increases in median levels of interleukin-8 and monocyte chemoattractant protein-1 BAL fluid were detected.Conclusions: These findings support the contention that interleukin-12 plays a role in the modulation of the local pro-/anti-fibrotic balance of allograft airways. [Copyright &y& Elsevier]

: Background:Encouraging results in transplantation of other solid organs led to investigation of the use of tacrolimus in lung transplantation as a salvage immunosuppressant in persistent acute rejection.: Methods:The incidence and severity of acute rejection and the number of steroid pulses were analyzed in 20 lung recipients who were converted from a cyclosporine- to a tacrolimus-based immunosuppressive regimen because of refractory biopsy-proven acute rejection.: Results:Tacrolimus was started 12.0 ± 13.0 months after transplantation, and the mean follow-up was 25.0 ± 13.7 months. After shifting to tacrolimus, a significant decline was observed in both the number of acute rejections per patient (3.0 ± 1.56 to 0.85 ± 1.14, p < 0.0001), and the incidence of acute rejection per 100 patient-days (1.52 ± 0.99 to 0.14 ± 0.21, p < 0.0001). Furthermore, the average histologic grade of rejection decreased from 1.9 ± 0.8 to 0.4 ± 0.5 (p < 0.0001). Methylprednisolone pulses similarly decreased from 1.9 ± 1.3/patient to 0.3 ± 0.7/patient (p < 0.0001). During cyclosporine immunosuppression, the mean forced expiratory volume in 1 second decreased to 84.4% ± 13.3% of individual best value. The average lung function parameters were stable 3 months after the change of medication, and then began to improve. After an average follow-up of 36.5 ± 19.2 months, 2 patients have developed bronchiolitis obliterans syndrome (one has Stage 1 and one has Stage 3).: Conclusions:Conversion to a tacrolimus-based immunosuppressive regimen for refractory acute lung rejection is associated with reduced incidence and severity of acute rejection episodes, steroid sparing, and stabilization or improvement of pulmonary function. [Copyright &y& Elsevier]

Recombinant granulocyte colony-stimulating factor (rG-CSF) is a myeloid growth factor that is widely used in haematology to recover neutropenia secondary to myelosuppressive chemotherapy. Leukocytoclastic vasculitis is an acknowledged side effect of the above therapy. Its pathogenesis involves many mechanisms that collectively induce an increase in neutrophil function and a subsequent release of cytokines. Here, we report a case of leukocytoclastic vasculitis proven by skin biopsy, following the use of rG-CSF in a heart transplant patient with leukopenia secondary to immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Grover's disease is a transient acantholytic dermatosis of unknown cause, manifesting clinically as a papular skin eruption that is usually located on the anterior chest and abdomen. Histologically characterized by an acantholytic pattern, it has been associated with numerous disorders, including hematologic malignancies, chronic renal failure, and HIV infection, as well as with chemotherapy and bone marrow and/or kidney transplant. Evaluation of followup and treatment is often complicated by spontaneous remission and the occasionally fluctuant course of the disease. Here we report the case of a patient with sudden onset of Grover's disease after heart transplantation. To the best of our knowledge, this is the first observation of Grover's disease as diagnosed after heart transplantation. [ABSTRACT FROM AUTHOR]

The pharmacokinetic properties of immunosuppressive drugs are quite different in newborns than in adults and few studies describe the pharmacokinetics of these drugs in pediatric heart transplant recipients. We report on the two-year follow up of a neonate who underwent heart transplantation for Hypoplastic Left Heart Syndrome on day of life 9. Two different immunosuppressive regimens were used: cyclosporine, azathioprine and prednisone in the early postoperative period, followed by the routine tacrolimus and mycophenolate mofetil combination plus prednisone from post-transplant day 22. Our findings demonstrate marked variability in immunosuppressive pharmacokinetic profiles early post-transplant. Frequent monitoring of drug levels is required to ensure that they remain within the therapeutic range. After the first 2-3 months post-transplant, changes in immunosuppressive drug levels are less marked and correlate more with the administered dosage. [ABSTRACT FROM AUTHOR]

The minimally invasive Heartport (HP)-assisted technique has become first choice option for mitral valve surgery in many centres. The pool of patients potentially treated using HP techniques, however, is still limited by the presence of peripheral vessel disease, expecially in the elderly population. Alternative approaches to using the HP technique safely in such a subset of patients, therefore, should be evaluated. Here, we present our preliminary experience using the axillary artery as an alternative site of cannulation for HP-assisted redo mitral valve surgery in patients with concomitant peripheral vessel disease. [ABSTRACT FROM AUTHOR]

The pharmacokinetic properties of immunosuppressive drugs are quite different in newborns than in adults and few studies describe the pharmacokinetics of these drugs in pediatric heart transplant recipients. We report on the two-year follow up of a neonate who underwent heart transplantation for Hypoplastic Left Heart Syndrome on day of life 9. Two different immunosuppressive regimens were used: cyclosporine, azathioprine and prednisone in the early postoperative period, followed by the routine tacrolimus and mycophenolate mofetil combination plus prednisone from post-transplant day 22. Our findings demonstrate marked variability in immunosuppressive pharmacokinetic profiles early post-transplant. Frequent monitoring of drug levels is required to ensure that they remain within the therapeutic range. After the first 2-3 months post-transplant, changes in immunosuppressive drug levels are less marked and correlate more with the administered dosage. [ABSTRACT FROM AUTHOR]