Platelet reactivity in patients with acute coronary syndrome treated with prasugrel or ticagrelor in comparison to clopidogrel: a retrospective pharmacodynamic analysis.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a mainstay of the prevention of stent thrombosis following percutaneous coronary intervention (PCI). In the 2015 European guidelines for the management of acute coronary syndrome (ACS), prasugrel (PRA) and ticagrelor (TICA) combined with aspirin are recommended as first-line therapy. Clopidogrel (CLO) is recommended as an alternative medication for patients with contradictions to these new drugs. This single-center study analyzed the platelet function of 809 ACS patients undergoing PCI and treatment with DAPT. The platelet response to ADP was determined using Multiplate® analyzer at a median of 3 days after PCI in 254 patients treated with PRA (loading dose [LD] 60 mg, 10 mg qd), 162 patients receiving TICA (LD 180 mg, D 90 mg bid), and 393 CLO-treated patients (LD 600 mg, 75 mg qd). An aggregation >468 arbitrary units (AU)*min was defined as "high on-treatment platelet reactivity" (HPR), <188 AU*min as "low on-treatment platelet reactivity" (LPR). Platelet response in PRA-treated patients was lower compared to CLO or TICA (median; interquartile range: PRA 220 [163-275] AU*min vs. CLO 268 [186-387] AU*min, p < 0.001 vs. TICA 245 [190-320] AU*min, p = 0.001). Only 1.6% of PRA patients were stratified as HPR and 34.6% as LPR, while in the TICA group 1.9% fulfilled the criteria of HPR and 24.1% criteria of LPR. Sixteen percent of CLO patients were stratified as HPR and 26.2% as LPR. In a real-world cohort of ACS patients following PCI, PRA results in more potent inhibition of platelet function compared to CLO and TICA. TICA achieves a consistent antiplatelet effect with reduced rates of HPR and LPR in relation to CLO.

Magnetic resonance myocardial perfusion imaging at 3.0 Tesla for the identification of myocardial ischaemia: comparison with coronary catheter angiography and fractional flow reserve measurements.

AIMS: To assess image quality and diagnostic performance of 3.0 Tesla (3T) cardiac magnetic resonance (CMR) myocardial perfusion imaging with a dual radiofrequency source to detect functional relevant coronary artery disease (CAD), using coronary angiography and invasive pressure-derived fractional flow reserve (FFR) as reference standard. METHODS AND RESULTS: We included 116 patients with suspected or known CAD, who underwent 3T adenosine myocardial perfusion CMR (resolution 2.97 × 2.97 mm) and coronary angiography plus FFR measurements in intermediate lesions. Image quality of myocardial perfusion CMR was graded on a 4-point scale (1 = poor to 4 = excellent). Diagnostic accuracy was assessed by ROC analyses using a 16-myocardial segment-based summed perfusion score (0 = normal to 3 = transmural perfusion defect) and by determining sensitivity, specificity, positive and negative predictive value on the coronary vessel territory and the patient level. Diagnostic image quality was achieved for all stress myocardial perfusion CMR studies with an average quality score of 2.5, 3.1, and 3.0 for LAD, LCX, and RCA territories. The ability of the myocardial perfusion CMR perfusion score to detect significant coronary artery stenosis yielded an area under the curve of 0.93 on ROC analysis. Values for sensitivity, specificity, positive and negative predictive value on a vessel territory level and the patient level were 89, 95, 87, 96% and 85, 87, 77, 92%, respectively. CONCLUSION: In patients with suspected or known significant CAD, 3T myocardial perfusion CMR with standard perfusion protocols provides consistently high image quality and an excellent diagnostic performance.

Simultaneous carotid endarterectomy and cardiac surgery: early results of 386 patients.

BACKGROUND: The occurrence of severe carotid artery disease in more than 12% of patients requiring coronary artery bypass grafting (CABG) results in a discrepancy concerning best treatment for both diseases. We reviewed the early outcome of patients with CABG and/or valve replacement (VR) and simultaneous carotid endarterectomy (CEA). METHODS: We retrospectively evaluated 386 patients after simultaneous operation between 7/1994 and 9/2010. Total 326 patients received isolated CABG, 56 CABG and/ or VR, 4 aortic surgery. Mean age was 68.3 years (range: 45 to 87). Male patients were 229. Severity of stenosis at operated side was 70 to 80% in 167, 80 to 99% in 219 patients. Total 164 patients showed bilateral carotid stenosis, 32 had contralateral occlusion. We analyzed risk factors, morbidity, incidence of neurological events, and 30-day mortality. RESULTS: Perioperative stroke with hemiplegia occurred in 10 patients (2.6%). Three patients experienced PRIND, seven TIA. A 30-day mortality was 5.2%. Total 8 deaths were cardiac related, 10 due to extracardial reasons, and 2 patients developed a cerebral death. CONCLUSIONS: Simultaneous CEA and cardiac surgery can be performed with a low risk for neurological complications and acceptable mortality. Occlusion of contralateral carotid artery could be identified as an evident predictor for increased neurological complications.

Fecal calprotectin is a useful screening parameter for hepatic encephalopathy and spontaneous bacterial peritonitis in cirrhosis.

OBJECTIVE: Bacterial translocation, causing intestinal inflammation, is one of the key mechanisms in the pathogenesis of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP) The presence of fecal calprotectin quantitatively relates to intestinal neutrophil migration and is therefore considered as a marker of intestinal inflammation. We aimed to assess the role of fecal calprotectin concentrations (FCCs) in diagnosing the onset and severity of HE and SBP. METHODS: Sixty-one cirrhotics were prospectively included. Forty-two subjects served as controls. Several complications of cirrhosis were diagnosed by reference methods. Stool samples were collected for measuring FCCs. Patients revealing other causes of abnormal calprotectin results, e.g. gastrointestinal bleeding or inflammatory bowel disease were excluded. Multivariate analysis of cirrhosis-associated complications and their relation to FCCs was performed. RESULTS: Fecal calprotectin concentrations were higher in cirrhotics compared with controls (P<0.001). Among cirrhotics, FCCs were elevated dependent on the severity of liver disease as assessed by Child- and model for end-stage liver disease-scores. The corresponding correlation co-efficients by Spearman's were 0.577 (P<0.001) and 0.303 (P=0.018) respectively. A correlation emerged between elevated FCCs and HE grading as measured by West-Haven criteria and critical flicker frequency (both P<0.001; sensitivity=0.94 and 0.93, specificity=0.95 and 0.89 respectively) and SBP (P<0.02; sensitivity=0.71, specificity=0.79). FCCs were higher in cirrhotic subjects with additional extra-intestinal inflammation (P<0.01; sensitivity=0.65, specificity=0.8). The Pearsons correlation coefficients were 0.190 and 0.164 revealing no influence (P=0.142 and P=0.207) of laboratory parameters of systemic inflammation on FCCs in cirrhotic subgroup. CONCLUSIONS: Fecal calprotectin concentrations serve as a screening tool for HE and SBP. Assessment of FCCs may faciliate grading of HE-severity.

Nonhepatic cancer in liver cirrhosis: a retrospective study of prevalence, complication rate after specific oncological treatment, follow-up and prognostic predictors of outcome in 354 patients with cirrhosis.

BACKGROUND: Nonhepatic cancer risk of cirrhotic patients seems to be increased. Major surgery and chemotherapy in cirrhosis are associated with increased mortality and morbidity, which limits treatment. AIM: The aims of this study were analysis of (a) prevalence, (b) outcome after treatment, (c) of survival rate and (d) predictors of survival in a cirrhotic population. PATIENTS AND METHODS: The study population was assembled retrospectively from a database of hospitalized patients (n=354). The Kaplan-Meier method was used to calculate the survival rate, and Cox regression analysis was performed to identify prognostic parameters. RESULTS: Altogether, 84 neoplasms in 70 patients were observed. A total of 54 were nonhepatic (15.3%) mainly colorectal carcinoma, prostate cancer and tobacco-related neoplasms. TNM stage was the best prognostic parameter (p<0.0001). Low bilirubin (p=0.01), normal albumin (p=0.005) and absence of ascites (p<0.0001) were also related significantly to longer survival. The rate of postinterventional death after specific treatment was high. A proportion of patients received no specific therapy due to reduced physical performance, even in cases of limited disease. CONCLUSION: Our data confirm the increased risk of cirrhotic patients for developing nonhepatic cancer. Advanced TNM stage was associated with reduced long-term survival. Scoring systems, such as Child's classification and Model of Elevated Liver Disease (MELD) score, were suitable parameters to predict mortality. Oncological management in patients with cirrhosis must be on an individual basis, independent from TNM classification.

Early and late outcomes of cardiac operations in patients with cirrhosis: a retrospective survival-rate analysis of 47 patients over 8 years.

OBJECTIVES: Patients with liver cirrhosis are considered as high-risk population for cardiac surgery. The aim of this study was to review mortality and mid-term outcome of patients with liver cirrhosis requiring coronary artery bypass graft (CABG), valve replacement, or combined procedures. METHODS: Between July 1997 and December 2006, 47 patients (mean age 65.4 ± 11.7 years) with liver cirrhosis were operated for CABG (21 patients), aortic valve replacement /mitral valve replacement (14 patients), CABG/VR (9 patients) or aortic dissection/tumorexstirpation (3 patients) (group I). Thirty-three patients were classified as Child-Pugh class A (subgroup A), 14 patients as Child-Pugh class B cirrhosis (subgroup B). Postoperative complications/mortality were analyzed retrospectively and compared with a propensity-score pair-matched control group of 47 patients (group II). Follow-up ranged from 0.1 to 11.5 years (mean 3.9 ± 0.25 years) and was complete for 100%. RESULTS: Necessity of blood products was higher in group I (red cells, fresh frozen plama, platelets; P < 0.01). Chest-tube output (group I 1113 ± 857 vs. group II 849 ± 521; P = 0.15) and re-exploration rate (8.5 vs. 0%; P = 0.11) were slightly accelerated. Ventilation time and ICU-stay was prolonged (P < 0.015). Thirty-day mortality showed 19.1% (group I) versus 8.5% (group II) (P < 0.01), 6.1% (subgroup A) versus 50% (subgroup B) (P < 0.01). Operative risk in subgroup A was not significantly increased compared with control group (P = 0.68). In Child-B operative risk was 15.5-fold higher than in Child-A cirrhosis (P < 0.001). Postcardiotomy syndrome and pleurisy were more frequent in the cirrhosis group (4/47 vs. 0/47; P = 0.11). Actuarial survival after 3, 5 and 8 years was: group I 78.6, 75.6, and 70.2% versus group II 89.1, 85.7, and 85.7% (P = 0.08). Subgroup survival analysis was: group A 90.7, 86.6, and 78.5% versus group B 50, 50, and 50% (P < 0.01). CONCLUSION: Cardiac surgery can be performed safely in patients with Child-Pugh class A and selected patients with Child-Pugh class B cirrhosis. Mid-term survival-rates within 8 years were not significantly different compared with a propensity-score pair-matched control group without cirrhosis.

Quality of internal thoracic artery grafts after mediastinal irradiation.

BACKGROUND: With the increase of patients of advanced age requiring coronary artery bypass grafting (CABG), the number of those with previous mastectomy and irradiation of the chest increases proportionally. The question of whether mediastinal irradiation leads to relevant internal thoracic artery (ITA) graft damage remains unclear. The aim of the present study was to proof the quality of ITAs and to evaluate the early clinical outcome after using one or both ITAs in this specific population. METHODS: One hundred twenty-five patients (group A) with previous mastectomy or Hodgkin/non-Hodgkin disease and mediastinal irradiation operated on between January 1993 and September 2006 underwent CABG (n = 88) or CABG plus valve replacement (n = 37). Sixty-two patients received bilateral, 43 received unilateral ITAs, and 20 patients received veins. Postoperative complications and mortality were analyzed and compared with a propensity score pair-matched control group of 125 patients receiving CABG or CABG plus valve replacement within the same period (group B). A histomorphologic investigation was performed in 133 irradiated distal ITA segments and compared with a control group of 133 nonirradiated ITAs. RESULTS: Thirty-day mortality revealed 3.2% in group A versus 5.6% in group B. Sternal instabilities were more frequent in group A (3.2%) than in group B (0%). Mediastinitis occurred in 1.6% (group A) versus 1.6% (group B). Histomorphologic investigations did not identify any severe irradiation induced fibrosis or damage of ITA grafts. CONCLUSIONS: From the histologic point of view, there is no need for restrictions in use of ITA conduits after mediastinal irradiation. Compared with a control group, cardiac surgery was associated with a slightly enhanced incidence of sternal instabilities.

Does bilateral ITA grafting increase perioperative complications? Outcome of 4462 patients with bilateral versus 4204 patients with single ITA bypass.

OBJECTIVE: Superior patency of internal thoracic artery (ITA) grafting to saphenous veins is conclusive. The aim of the present study was to compare the early outcome of patients receiving either bilateral ITA (BITA) or single ITA (SITA) grafts and to identify risk factors for perioperative complications, such as obesity, diabetes mellitus, or advanced age. METHODS: All 8666 patients with isolated coronary artery bypass grafting (CABG, including emergent cases or redos) operated between January 1994 and June 2004 receiving either BITA (n=4462) or SITA (n=4204) grafting were analyzed retrospectively. Demographic data were comparable for both groups concerning mean age (65.3+/-9.4 years vs 64.9+/-9.3 years), range (35-89 years (p=0.05)), diabetes incidence (29.3% vs 2.6% (p=0.08)), dialysis-dependent renal failure (0.7% vs 0.6% (p=0.4)), preoperative ejection fraction (EF) mean (61.8% vs 61.2% (p=0.07)) but not for gender (80.4% vs 76.7% males (p=0.00)), body mass index (BMI) mean (27.2+/-3.6 vs 26.9+/-3.5 (p=0.00)), COPD (7.0% vs 8.5% (p=0.00)), and hyperlipidemia (78.3% vs 74.3% (p=0.00)). In the BITA group, right ITA (RITA) was directed preferentially to the left anterior descending artery (LAD), left ITA (LITA) to the lateral wall. In the SITA group, the LAD was revascularized with the left ITA. Additional bypasses were performed with saphenous vein grafts (SVG). RESULTS: The number of anastomoses was higher in the BITA group (3.8+/-0.9 vs 3.1+/-0.9 (p=0.00)); therefore, duration of surgery (mean: 189+/-46.3 min vs 164+/-46.2 min) and cross-clamp time (62.0+/-17.9 min vs 51.0+/-18.0 min) significantly prolonged (p=0.00). Incidence of rethoracotomy due to bleeding (2.9% vs 0.6%; p=0.00) or sternal refixation with (0.7% vs 0.2%; p=0.00) or without infection (1.4% vs 0.6%; p=0.00) was higher in the BITA group, strongly associated with diabetes mellitus and duration of surgery but not with BMI>27. Thirty-day mortality revealed 2.6% versus 3.2% (p=0.1) but was significantly lower for diabetic patients in the BITA group (3.1% vs 4.7%; p=0.00). CONCLUSIONS: CABG using both ITAs can be performed routinely with good clinical results and low mortality. Compared with single ITA grafting, sternal and bleeding complications were slightly increased. Diabetes mellitus, BITA grafting, duration of surgery but not obesity or COPD could be identified as independent risk factors for sternal complications. Dialysis-dependent renal failure, EF<30%, emergent cases, and the absence of BITA grafting were predictors for increased perioperative mortality.