Reduced force of diaphragm muscle fibers in patients with chronic thromboembolic pulmonary hypertension.

Patients with pulmonary hypertension (PH) suffer from inspiratory muscle weakness. However, the pathophysiology of inspiratory muscle dysfunction in PH is unknown. We hypothesized that weakness of the diaphragm, the main inspiratory muscle, is an important contributor to inspiratory muscle dysfunction in PH patients. Our objective was to combine ex vivo diaphragm muscle fiber contractility measurements with measures of in vivo inspiratory muscle function in chronic thromboembolic pulmonary hypertension (CTEPH) patients. To assess diaphragm muscle contractility, function was studied in vivo by maximum inspiratory pressure (MIP) and ex vivo in diaphragm biopsies of the same CTEPH patients (N = 13) obtained during pulmonary endarterectomy. Patients undergoing elective lung surgery served as controls (N = 15). Muscle fiber cross-sectional area (CSA) was determined in cryosections and contractility in permeabilized muscle fibers. Diaphragm muscle fiber CSA was not significantly different between control and CTEPH patients in both slow-twitch and fast-twitch fibers. Maximal force-generating capacity was significantly lower in slow-twitch muscle fibers of CTEPH patients, whereas no difference was observed in fast-twitch muscle fibers. The maximal force of diaphragm muscle fibers correlated significantly with MIP. The calcium sensitivity of force generation was significantly reduced in fast-twitch muscle fibers of CTEPH patients, resulting in a ∼40% reduction of submaximal force generation. The fast skeletal troponin activator CK-2066260 (5 µM) restored submaximal force generation to levels exceeding those observed in control subjects. In conclusion, diaphragm muscle fiber contractility is hampered in CTEPH patients and contributes to the reduced function of the inspiratory muscles in CTEPH patients.

Evaluating the endoscopic reference score for eosinophilic esophagitis: moderate to substantial intra- and interobserver reliability.

BACKGROUND AND STUDY AIMS: Recently the Endoscopic Reference Score (EREFS) for endoscopic assessment of eosinophilic esophagitis was introduced, with good interobserver agreement for most signs. The EREFS has not yet been evaluated by other investigators and intraobserver agreement has not been assessed. The aim of this study was to further validate the EREFS by assessing interobserver and intraobserver agreement of endoscopic signs in patients with eosinophilic esophagitis. PATIENTS AND METHODS: High-quality endoscopic images were made of the esophagus of 30 patients with eosinophilic esophagitis (age 36 years, range 23 - 46 years; 5 female), 6 of whom were in remission. At least three depersonalized images per patient were incorporated into a slideshow. Images were scored by four expert and four trainee endoscopists who were blinded to the patients' conditions. Interobserver agreement was assessed. After 4 weeks, the images were rescored in a different order to assess intraobserver agreement. RESULTS: Interobserver agreement was substantial for rings (κ 0.70), white exudates (κ 0.63), and crepe paper esophagus (κ 0.62), moderate for furrows (κ 0.49) and strictures (κ 0.54), and slight for edema (κ 0.12). Intraobserver agreement was substantial for rings (median κ 0.64, IQR 0.46 - 0.70), furrows (median κ 0.69, IQR 0.50 - 0.89), and crepe paper esophagus (median κ 0.69, IQR 0.62 - 0.83), moderate for white exudates (median κ 0.58, IQR 0.54 - 0.71) and strictures (median κ 0.54, IQR 0.33 - 0.70), and less than chance for edema (median κ 0.00, IQR 0.00 - 0.29). Inter- and intraobserver agreement was not substantially different between expert and trainee endoscopists. CONCLUSIONS: Using the EREFS, endoscopic signs of eosinophilic esophagitis were scored consistently by expert and trainee endoscopists.

The role of recalibration response shift in explaining bodily pain in cancer patients undergoing invasive surgery: an empirical investigation of the Sprangers and Schwartz model.

OBJECTIVE: This study aims to explain bodily pain using the Sprangers and Schwartz theoretical model (1999) on quality of life (QL) and response shift in its entirety. Response shift refers to the phenomenon that the meaning of a person's self-evaluation changes over time. In this model, response shift mediates effects of changes in health status (catalysts), stable characteristics of the person (antecedents), and coping mechanisms (mechanisms) on QL. METHODS: Cancer patients (202) were assessed prior to and 3 months following surgery. Measures were for catalysts: type of operation and possibility of tumor resection; for antecedents: age, duration of pain, optimism, and rigidity; for mechanisms: post-traumatic growth, social comparisons, social support, denial, and acceptance; and for QL: bodily pain; for response shift: the pretest-minus-thentest bodily pain score, further referred to as recalibration response shift. Structural equation modeling and sequential regression analyses were used. RESULTS: The final model reached close fit (RMSEA = 0.03; 90% CI = 0.000-0.071; χ2 (18) = 21.13; p = 0.27). Significant effects were found for catalysts on mechanisms, antecedents on mechanisms, mechanisms on response shift, and response shift on bodily pain. Four extra model effects had to be permitted. Using sequential regression analysis, recalibration response shift added 4.4% to the total amount of 29.8% explained variance of bodily pain. CONCLUSIONS: Many effects as hypothesized by the model were found. Recalibration response shift had a unique albeit small contribution to the explanation of bodily pain.

Pulmonary endarterectomy normalizes interventricular dyssynchrony and right ventricular systolic wall stress.

BACKGROUND: Interventricular mechanical dyssynchrony is a characteristic of pulmonary hypertension. We studied the role of right ventricular (RV) wall stress in the recovery of interventricular dyssynchrony, after pulmonary endarterectomy (PEA) in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: In 13 consecutive patients with CTEPH, before and 6 months after pulmonary endarterectomy, cardiovascular magnetic resonance myocardial tagging was applied. For the left ventricular (LV) and RV free walls, the time to peak (Tpeak) of circumferential shortening (strain) was calculated. Pulmonary Artery Pressure (PAP) was measured by right heart catheterization within 48 hours of PEA. Then the RV free wall systolic wall stress was calculated by the Laplace law. RESULTS: After PEA, the left to right free wall delay (L-R delay) in Tpeak strain decreased from 97 ± 49 ms to -4 ± 51 ms (P < 0.001), which was not different from normal reference values of -35 ± 10 ms (P = 0.18). The RV wall stress decreased significantly from 15.2 ± 6.4 kPa to 5.7 ± 3.4 kPa (P < 0.001), which was not different from normal reference values of 5.3 ± 1.39 kPa (P = 0.78). The reduction of L-R delay in Tpeak was more strongly associated with the reduction in RV wall stress (r = 0.69,P = 0.007) than with the reduction in systolic PAP (r = 0.53, P = 0.07). The reduction of L-R delay in Tpeak was not associated with estimates of the reduction in RV radius (r = 0.37,P = 0.21) or increase in RV systolic wall thickness (r = 0.19,P = 0.53). CONCLUSION: After PEA for CTEPH, the RV and LV peak strains are resynchronized. The reduction in systolic RV wall stress plays a key role in this resynchronization.

Time course of restoration of systolic and diastolic right ventricular function after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

BACKGROUND: In chronic thromboembolic pulmonary hypertension, right ventricular (RV) pressure overload causes RV remodeling and dysfunction. Successful pulmonary endarterectomy (PEA) initiates restoration of RV remodeling and global function. Little is known on the restoration of systolic and diastolic RV function. Using transthoracic echocardiography, we studied the time course and extent of postoperative restoration of systolic and diastolic RV function. METHODS: In chronic thromboembolic pulmonary hypertension (n = 55, 36 women, age 52 ± 14 years), transthoracic echocardiography was performed before PEA (pre-PEA) and 2 weeks, 3 months, and 1 year postoperatively. RESULTS: Two weeks postoperatively, RV afterload and dimension had decreased significantly, without further improvement during follow-up. Global RV function, expressed by the myocardial performance index, showed a gradual improvement (from pre-PEA 0.58 ± 0.29 to 0.45 ± 0.38, 0.39 ± 0.19, and 0.37 ± 0.18). In contrast, 2 weeks after PEA systolic RV function, as assessed by tricuspid annular plane systolic velocity excursion and peak tricuspid annular systolic velocity of the RV, had worsened, with a subsequent incomplete restoration during follow-up: tricuspid annular plane systolic velocity excursion from 19.3 ± 5.0 to 12.4 ± 2.5, 15.3 ± 3.0, and 16.8 ± 2.9 mm and systolic velocity of the right ventricle from 11.4 ± 3.0 to 9.6 ± 2.0, 10.0 ± 1.8, and 10.3 ± 1.7 cm/s. Postoperative diastolic RV function also showed a biphasic response: tricuspid inflow-to-annulus ratio from 6.1 ± 3.0 to 9.5 ± 3.5, 6.8 ± 2.4, and 6.3 ± 2.2 cm/s. Dynamics and ultimate level of restoration of systolic and diastolic RV function were similar in patients with and without residual pulmonary hypertension. CONCLUSIONS: Postoperative reduction in RV afterload caused an immediate improvement in RV dimension and global function. In contrast, systolic and diastolic RV function deteriorated after PEA with subsequently a gradual yet incomplete restoration during 1-year follow-up.

Reversal of hepatic steatosis by omega-3 fatty acids measured non-invasively by (1) H-magnetic resonance spectroscopy in a rat model.

BACKGROUND AND AIM: Living donors with marked (> 33%) macrovesicular steatosis (MaS) are excluded from living donor liver transplantation procedures. Experimental studies have shown that the development of steatosis can be prevented by supplementation with omega-3 fatty acids (FA), but no studies have investigated the reduction of steatosis using omega-3 FA. The aim of the present study was to investigate whether administration of omega-3 FA is effective in reducing steatosis. METHODS: After fatty liver (FL) induction by a 3-week methionine/choline-deficient (MCD) diet, male Wistar rats were daily administered per gavage omega-3 FA (FL+Omega-3), omega-3-poor lipid solution (FL+Lipid), or NaCl (FL+NaCl) during 2 weeks. Control animals received standard chow without treatment. Determination of steatosis degree was performed before, during, and after treatment by clinical 3.0 T ¹H-magnetic resonance spectroscopy (¹H-MRS) and by histology and gas chromatography at the end of the 2-week treatment period. RESULTS: Hepatic fat content (¹H-MRS) was significantly reduced after 1 and 2 weeks of omega-3 FA treatment. Histological analysis revealed a mild (5-33%) MaS degree in omega-3-treated animals vs severe (> 66%) MaS in the FL+Lipid and FL+NaCl groups. Hepatic omega-6 : 3 FA ratio and total FA content were reduced in the FL+Omega-3 group. Furthermore, de novo lipogenesis (C16, C16 : 1ω7, C18 : 1ω9) was also lowered. The reduction in hepatic fat content was associated with decreased lobular inflammation and hepatic tumor necrosis factor- α and interleukin levels as well as an increased antioxidative capacity. CONCLUSION: Omega-3 FA are capable of reversing severe hepatic MaS and ameliorating pathophysiological features of non-alcoholic steatohepatitis such as hepatocellular damage, lobular inflammation, and a reduced antioxidative capacity.

Long-term follow-up after nonurgent percutaneous coronary intervention in unprotected left main coronary arteries.

OBJECTIVES: To evaluate the long-term outcomes of the selected patients by the local Heart Team to undergo percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) stenosis and to compare patients considered at low surgical risk versus at high surgical risk for coronary artery bypass grafting (CABG). BACKGROUND: CABG is recommended in patients with ULMCA stenosis according to the AHA/ACC and ESC guidelines, and there are limited data on the long-term outcomes in patients selected by the local Heart Team to undergo PCI. METHODS: Between 1996 and 2007, 227 patients underwent PCI for ULMCA stenosis based on decision of the local Heart Team and patient's and/or physician's preference. All patients were contacted at 1 year and in November 2008. RESULTS: Long-term follow-up was up to 8 years with a mean of 3.9 +/- 2.6 years. Overall, the Kaplan-Meier estimate of the composite of cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR) was 14.8% at 1 year, 18.3% at 3 years, and 20.9% at 5 years with no events occurring thereafter. Patients considered at low surgical risk for CABG had a significantly lower incidence of cardiac death or MI compared to patients considered at high surgical risk at 8 years (1.4 vs. 16.8%; 1.4 vs. 14.8%, respectively); however, no significant difference was observed for cardiac death, MI, or TLR (18.6 vs. 24.4%). CONCLUSIONS: PCI of ULMCA stenosis in patients selected by the Heart Team resulted in good long-term clinical outcomes with most events occurring within the 1st year. Patients considered at low surgical risk for CABG have a significantly better long-term survival than patients at high risk for surgery.

Effect of preoperative biliary drainage on coagulation and fibrinolysis in severe obstructive cholestasis.

GOALS: To evaluate the function of coagulation and fibrinolysis in cholestatic patients before and after preoperative biliary drainage (PBD). BACKGROUND: Cholestasis owing to an obstructive biliary malignancy is associated with postoperative complications related to a proinflammatory state, an impaired hepatic synthesis function, and a potential derangement of hemostasis. Hence, PBD is advocated for cholestatic patients undergoing major surgery. STUDY: Plasma coagulation and fibrinolytic parameters were assessed in 24 cholestatic patients and 10 controls. In 9 cholestatic patients, the parameters were reassessed at least 4 weeks after PBD. RESULTS: Compared with controls, cholestatic patients showed lower concentrations (P<0.001) of plasma vitamin K-dependent factors II and VII, whereas prothrombin time, activated partial thromboplastin time, and factor V were unaltered. Thrombin generation was increased in cholestatic patients, as reflected by higher plasma concentrations of thrombin-antithrombin complexes and D-dimers. Fibrinolysis was significantly impaired as evidenced by low plasminogen activator activity (PAA) owing to an increase in plasminogen activator inhibitor -1). Elevated markers for thrombin generation thrombin-antithrombin decreased after PBD from 10.7±1.2 to 5.7±0.7 ng/mL (P<0.05). Additionally, impairment of fibrinolysis in cholestatic patients resolved after PBD (plasminogen activator inhibitor-1 levels decreased from 19±1 to 10±1 IU/mL and plasminogen activator activity increased from 82±3 to 110±4%, respectively). D-dimers remained unaltered after PBD, likely because of normalization of coagulation and fibrinolytic activity. CONCLUSIONS: Obstructive cholestasis is associated with a procoagulant state, despite an impaired vitamin K-dependent coagulation factor synthesis. Virtually all alterations in coagulation and fibrinolysis were reversed by biliary drainage.

The influence of provider characteristics on resection rates and survival in patients with localized non-small cell lung cancer.

Surgery remains the mainstay of treatment for localized non-small cell lung cancer (NSCLC). However, wide variations have been reported regarding rates of operative therapy. We examined the influence of characteristics of the hospital of diagnosis on the likelihood of receiving surgical treatment and on survival. We evaluated patients with primary, first-time, localized NSCLC diagnosed from 1998 to 2003 in the region of the Amsterdam Cancer Registry. Treatment and survival data were extracted from the registry database. We investigated which provider characteristics (hospital category, mean annual lung cancer caseload, presence of a cardiothoracic surgery unit) were predictive of receiving surgical treatment and of survival. 1591 patients were diagnosed with clinically localized NSCLC, of which 1097 (69%) had surgery. Resection rates varied significantly between the various hospitals (48-90%, chi(2), P<0.001). Patients diagnosed at specialized centers or higher volume hospitals were more likely to receive surgical therapy, especially for patients over 80 years of age. In addition, there was a trend that octogenarians had higher odds of undergoing surgery when diagnosed in a center with a cardiothoracic surgery unit. Patients had a better survival after resection than without surgery (P<0.001). Survival after surgery did not differ between the various hospital categories. In conclusion, there is wide institutional variability in rates of surgical treatment in lung cancer patients. In addition to patient characteristics, attributes of the hospital of diagnosis also have significant influence on the likelihood of receiving surgical therapy. Future studies should examine the underlying mechanisms for this phenomenon.

Differentiation of malignant and benign proximal bile duct strictures: the diagnostic dilemma.

AIM: To identify the criteria for the differentiation of hilar cholangiocarcinoma (HCCA) from benign strictures. METHODS: A total of 68 patients underwent resection of lesions suspicious for HCCA between 1998 and 2006. The results of laboratory investigations, imaging studies and brush cytology were collected. These findings were analyzed to obtain the final diagnosis. RESULTS: Histological examination of the resected specimens confirmed HCCA in 58 patients (85%, group I) whereas 10 patients (15%, group II) were diagnosed to have benign strictures. The most common presenting symptom was obstructive jaundice in 77% patients (79% group I vs 60% group II, P = 0.23). Laboratory findings showed greater elevation of transaminase levels in group I compared to group II. The various imaging modalities showed vascular involvement exclusively in the malignant group (36%, P < 0.05). Brush cytology was positive for malignant cells in only 50% patients in group I whereas none in group II showed malignant cells. CONCLUSION: Despite improvements in imaging techniques, 10 patients (15%) with a presumptive diagnosis of HCCA were ultimately found to have benign strictures. Except for vascular involvement which was associated significantly with malignancy, there were no conclusive features of malignancy on regular imaging modalities. This uncertainty should be taken into account when patients with a suspicious lesion at the liver hilum are considered for resection.

Open window thoracostomy: a new therapeutic option using topical negative pressure wound therapy.

Open window thoracostomy (OWT) is an invasive treatment option for thoracic empyema that is seldom indicated. These wounds are accompanied with a prolonged hospital stay and significant patient discomfort over an extended period of time. A retrospective report was conducted on patients who underwent OWT at the Academic Medical Center (Amsterdam, The Netherlands) and evaluated if topical negative pressure therapy ([TNP], V.A.C.® Therapy™, KCI Medical BV, Houten, The Netherlands) is a valid treatment option for these wounds. Clinical outcome and applied management methods are analyzed. Between January 1986 and June 2005, 15 patients, with a mean age of 54 years, were treated with OWT. Recently, the authors have used TNP in combination with OWT as a new treatment modality to obtain rapid control over pleural bacterial load and to achieve a well-vascularized wound surface. Good clinical results and a trend toward shorter hospital stays and improved quality of life were seen. Open window thoracostomy as a treatment modality for thoracic empyema is a valid option but only when other means fail or are contraindicated. Treatment of open window thoracostomy in combination with TNP is a safe and adequate therapeutic option for thoracic empyema resulting in improved quality of life and overall shorter hospital stay.

Hemodynamic and ventilatory responses during exercise in chronic thromboembolic disease.

BACKGROUND: Patients with chronic thromboembolic disease (CTED) may suffer from exercise intolerance without pulmonary hypertension at rest. Pulmonary endarterectomy (PEA) for symptomatic CTED results in improvement of symptoms and quality of life. Neither the pathophysiology of the exercise limitation nor the underlying mechanisms of the PEA-induced improvement have been studied previously. OBJECTIVES: We studied hemodynamic and ventilatory responses upon exercise in 14 patients with CTED. After 1 year, we studied the underlying physiologic mechanisms of the PEA-induced symptomatic improvement. METHODS: Cardiopulmonary exercise testing (CPET) was performed during right heart catheterization, and noninvasive CPET was performed 1 year postoperatively. RESULTS: During exercise, we observed abnormal pulmonary vascular responses, that is, a steep mean pulmonary artery pressure/cardiac output (2.7 ± 1.2 mm Hg·min·L(-1)), and low pulmonary vascular compliance (2.8 ± 1.1 mL·mm Hg(-1)); mean pulmonary artery pressure/cardiac output slope correlated with dead-space ventilation (r = 0.586; P = .028) and ventilatory equivalents for carbon dioxide slope (r = .580; P = .030). Postoperatively, the improvement observed in exercise capacity was related to improvements in CPET-derived parameters pointing to restoration of right ventricle stroke volume response (oxygen pulse: 11.7 ± 3.1 to 13.3 ± 3.3; P = .027; heart rate response: 80.9 ± 12.4 to 72.0 ± 5.7; P = .003); and, indicating improved ventilatory efficiency, the ventilatory equivalents for carbon dioxide slope decreased from 38.2 ± 3.6 to 32.8 ± 7.0 (P = .014). CONCLUSIONS: Patients with CTED showed an abnormal pulmonary vascular response to exercise and a decreased ventilatory efficiency. Responses after PEA point to restoration of right ventricle stroke volume response and ventilatory efficiency.

Simple steatosis sensitizes cholestatic rats to liver injury and dysregulates bile salt synthesis and transport.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder. It is uncertain if simple steatosis, the initial and prevailing form of NAFLD, sensitizes the liver to cholestasis. Here, we compared the effects of obstructive cholestasis in rats with a normal liver versus rats with simple steatosis induced by a methionine/choline-deficient diet. We found that plasma liver enzymes were higher and hepatic neutrophil influx, inflammation, and fibrosis were more pronounced in animals with combined steatosis and cholestasis compared to cholestasis alone. Circulating bile salt levels were markedly increased and hepatic bile salt composition shifted from hydrophilic tauro-ß-muricholate to hydrophobic taurocholate. This shift was cytotoxic for HepG2 hepatoma cells. Gene expression analysis revealed induction of the rate-limiting enzyme in bile salt synthesis, cytochrome P450 7a1 (CYP7A1), and modulation of the hepatic bile salt transport system. In conclusion, simple steatosis sensitizes the liver to cholestatic injury, inflammation, and fibrosis in part due to a cytotoxic shift in bile salt composition. Plasma bile salt levels were elevated, linked to dysregulation of bile salt synthesis and enhanced trafficking of bile salts from the liver to the systemic circulation.

Effect of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension on stroke volume response to exercise.

In pulmonary hypertension, exercise is limited by an impaired right ventricular (RV) stroke volume response. We hypothesized that improvement in exercise capacity after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is paralleled by an improved RV stroke volume response. We studied the extent of PEA-induced restoration of RV stroke volume index (SVI) response to exercise using cardiac magnetic resonance imaging (cMRI). Patients with CTEPH (n = 18) and 7 healthy volunteers were included. Cardiopulmonary exercise testing and cMRI were performed before and 1 year after PEA. For cMRI studies, pre- and post-operatively, all patients exercised at 40% of their preoperative cardiopulmonary exercise testing-assessed maximal workload. Post-PEA patients (n = 13) also exercised at 40% of their postoperative maximal workload. Control subjects exercised at 40% of their predicted maximal workload. Preoperatively, SVI (n = 18) decreased during exercise from 35.9 ± 7.4 to 33.0 ± 9.0 ml·m(2) (p = 0.023); in the control subjects, SVI increased (46.6 ± 7.6 vs 57.9 ± 11.8 ml·m(-2), p = 0.001). After PEA, the SVI response (ΔSVI) improved from -2.8 ± 4.6 to 4.0 ± 4.6 ml·m(2) (p <0.001; n = 17). On exercise at 40% of the postoperative maximal workload, SVI did not increase further and was still significantly lower compared with controls. Moreover, 4 patients retained a negative SVI response, despite (near) normalization of their pulmonary hemodynamics. The improvement in SVI response was accompanied by an increased exercise tolerance and restoration of RV remodeling. In conclusion, in CTEPH, exercise is limited by an impaired stroke volume response. PEA induces a restoration of SVI response to exercise that appears, however, incomplete and not evident in all patients.

Bosentan treatment is associated with improvement of right ventricular function and remodeling in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Medical pretreatment before pulmonary endarterectomy (PEA) can optimize right ventricular (RV) function and may improve postoperative outcome in high-risk patients. Using cardiac magnetic resonance imaging (cMRI), we determined whether the dual endothelin-1 antagonist bosentan improves RV function and remodeling in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who waited for PEA. HYPOTHESIS: We hypothesized that medical therapy prior to PEA will be associated with improvements in RV remodeling and function. METHODS: In this pilot study, 15 operable CTEPH patients were randomly assigned to either bosentan (n = 8) or no bosentan (n = 7, control) for 16 weeks, next to "best standard of care." Both before and after treatment, RV stroke volume index (RVSVI), RV ejection fraction (RVEF), RV mass, RV isovolumic relaxation time (rIVRT), leftward ventricular septal bowing (LVSB), and left ventricular ejection fraction (LVEF) were determined using cMRI. RESULTS: After 16 weeks, the change (Δ) from baseline (median [range]) in the studied cMRI parameters differed significantly between the bosentan group and the controls: Δ RVSVI: 6 [-4-11] vs 1 [-6-3] mL/m(-2) ; Δ RVEF: 8 [-10-15] vs -4 [-7-5]%; Δ RV mass: -3 [-6--2] vs 2 [-1-3] g/m(-2) ; Δ rIVRT: -30 [-130-20] vs 10 [-30-30] msec; Δ LVSB: 0.03 [-0.03-0.13] vs -0.03[-0.08-0.04] cm(-1) ; and Δ LVEF: 8 [-5-17] vs -2 [-14-2]% (all P < 0.05). The change from baseline in mean pulmonary artery pressure (-11 [-17-11] vs 5 [-6-21] mm Hg, P < 0.05) and 6-minute walk distance (20 [3-88] vs -4 [-40-40] m, P < 0.05) also differed significantly. CONCLUSIONS: In CTEPH, compared with control, treatment with bosentan for 16 weeks was associated with a significant improvement in cMRI parameters of RV function and remodelling.

Clinical outcome after surgical or percutaneous revascularization in coronary bypass graft failure.

AIMS: To describe long-term outcome following surgical and percutaneous revascularization in graft failure. METHODS: We analyzed consecutive patients with graft failure after heart-team assignment to percutaneous coronary intervention (PCI) or redo coronary artery bypass grafting (CABG) between 2003 and 2008. The primary endpoint was the composite of death, myocardial infarction (MI) or target vessel revascularization (TVR). Kaplan-Meier event rate estimates were calculated up to a 5-year follow-up. Independent predictors for outcomes were identified by backward selection in a multivariable Cox proportional hazard model. RESULTS: We identified 287 patients treated for graft failure: 243 with PCI and 44 with redo CABG. Patients undergoing PCI more frequently presented with ST-elevated myocardial infarction (STEMI) (P < 0.001), multivessel disease (P < 0.001), vein graft failure (P = 0.04), a history of MI (P < 0.001) and shorter time-to-graft failure (P = 0.001). Bare-metal stents (BMS) were used in 81.3% of the PCI-treated lesions and drug-eluting stents (DES) in 18.7%. The median follow-up was 3.9 years. Five-year rate of composite all-cause death, MI or TVR was 57.6% after PCI and 51% after CABG (P = 0.51). Repeat revascularization [TVR and target lesion revascularization (TLR)] was 30.7 and 21.3% after PCI, and 8.0 and 3.2% following CABG (P = 0.009; P = 0.008). In the PCI group, BMS was associated with higher rates of TVR (35.1 vs. 12.6%; P = 0.04) and TLR (24.8 vs. 7.6%; P = 0.04), but similar rate of death or MI compared with DES. Independent predictors for the primary outcome were creatinine [hazard ratio 1.008 per µmol/l, 95% confidence interval (CI) 1.005-1.011, P < 0.001] and peak creatine kinase MB (hazard ratio 1.001 per U/l, 95% CI 1.000-1.002, P = 0.027). CONCLUSION: Clinical outcomes are similarly poor after heart-team triage for surgical or percutaneous intervention in patients with graft failure. Repeat revascularization occurred more frequent after PCI, particularly following BMS implantation.

Clinical outcomes after percutaneous or surgical revascularisation of unprotected left main coronary artery-related acute myocardial infarction: a single-centre experience.

OBJECTIVES: We evaluated 30-day and 1-year clinical outcomes after percutaneous or surgical coronary revascularisation in patients with unprotected left main coronary artery (ULMCA)-related acute myocardial infarction (AMI). DESIGN: Single-centre registry. PATIENTS: Between January 1998 and December 2008, 84 patients with ULMCA-related AMI underwent revascularisation treatment in our institution (55 underwent percutaneous coronary intervention (PCI), 29 underwent coronary artery bypass graft surgery (CABG)). METHODS: One-year clinical follow-up was obtained for all patients. Univariable and multivariable analyses were performed to find predictors for 30-day mortality and treatment allocation. RESULTS: In the PCI-group, all-cause mortality was 64% at 30 days and 69% at 1 year. In the CABG-group, this was 24% at 30 days and 1 year. Independent predictors of 30-day mortality were cardiogenic shock (HR 2.83), thrombolysis in MI (TIMI) 0/1 flow (HR 2.27) and diabetes mellitus (HR 2.65). Treatment allocation to PCI was primarily determined by TIMI 0/1 flow on baseline angiogram (OR 150). In patients with TIMI 2/3 flow on initial angiogram, treatment allocation was determined by presentation with cardiogenic shock (OR 5.61), year of inclusion (OR 1.72), and distal/bifurcation disease (OR 0.11). CONCLUSIONS: Thirty-day mortality was high in patients presenting with an ULMCA-related AMI, both in the PCI as in the CABG-treatment group. Presentation with cardiogenic shock, TIMI 0/1 flow on initial angiogram and diabetes mellitus were independently predicting of 30-day mortality, whereas treatment allocation was primarily determined by presentation with TIMI 0/1 flow.

Plasma brain natriuretic peptide as a biomarker for haemodynamic outcome and mortality following pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

OBJECTIVES: In chronic thromboembolic pulmonary hypertension (CTEPH), right ventricular (RV) dysfunction is associated with increased morbidity and mortality following pulmonary endarterectomy. Plasma brain natriuretic peptide (BNP) levels were previously shown to correlate with RV (dys)function. We hypothesized that BNP can be used as a non-invasive biomarker to identify patients at 'high risk' for postoperative morbidity and mortality. METHODS: We studied the postoperative outcome in 73 consecutive patients. Patients were divided into three groups based on previously determined cut-off levels: BNP <11.5, indicating normal RV function (ejection fraction [EF] ≥45%), BNP >48.5 pmol/l, indicating RV dysfunction (right ventricular ejection fraction <30%) and BNP 11.5-48.5 pmol/l. Postoperative 'bad outcome' was defined as the presence of either residual pulmonary hypertension (PH) or (all-cause) mortality. RESULTS: Plasma BNP >48.5 pmol/l was shown to be an independent predictor of 'bad outcome'. Compared with BNP <11.5 pmol/l, BNP >48.5 pmol/l identified patients at higher risk for (all-cause) mortality (17 vs 0%; P = 0.009) and residual PH (56 vs 20%; P < 0.004). Also, the durations of mechanical ventilation and intensive care unit stay were significantly longer in patients with BNP >48.5 pmol/ml. CONCLUSIONS: Plasma BNP levels may be of use as a non-invasive biomarker reflecting RV dysfunction, next to other well-recognized (invasive) parameters, for better preoperative risk stratification of CTEPH patients.