Objectives

The aim of the work was to find biomarkers identifying patients at high risk of adverse clinical outcomes after TAVI and SAVR in addition to currently used predictive model (EuroSCORE).

Background

There is limited data about the role of biomarkers in predicting prognosis, especially when TAVI is available.

Methods

The multi-biomarker sub-study included 42 consecutive high-risk patients (average age 82.0 years; logistic EuroSCORE 21.0%) allocated to TAVI transfemoral and transapical using the Edwards-Sapien valve (n = 29), or SAVR with the Edwards Perimount bioprosthesis (n = 13). Standardized endpoints were prospectively followed during the 12-month follow-up.

Results

The clinical outcomes after both TAVI and SAVR were comparable. Malondialdehyde served as the best predictor of a combined endpoint at 1 year with AUC (ROC analysis) = 0.872 for TAVI group, resp. 0.765 (p<0.05) for both TAVI and SAVR groups. Increased levels of MDA, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase (TIMP1), ferritin-reducing ability of plasma, homocysteine, cysteine and 8-hydroxy-2-deoxyguanosine were all predictors of the occurrence of combined safety endpoints at 30 days (AUC 0.750–0.948; p<0.05 for all). The addition of MDA to a currently used clinical model (EuroSCORE) significantly improved prediction of a combined safety endpoint at 30 days and a combined endpoint (0–365 days) by the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) (p<0.05).

Cystatin C, glutathione, cysteinylglycine, asymmetric dimethylarginine, nitrite/nitrate and MMP9 did not prove to be significant. Total of 14.3% died during 1-year follow-up.

Conclusion

We identified malondialdehyde, a marker of oxidative stress, as the most promising predictor of adverse outcomes during the 30-day and 1-year follow-up in high-risk patients with symptomatic, severe aortic stenosis treated with TAVI. The development of a clinical “TAVIscore” would be highly appreciated. Such dedicated scoring system would enable further testing of adjunctive value of various biomarkers.

Purpose

To determine intraindividual variability in concentrations of homocysteine and related thiols in follicular fluids of particular follicles after ovarian stimulation and assess the differences between follicles with/or without oocytes.

Methods

HPLC-FD analysis of plasma and follicular fluid cysteine, homocysteine, cysteinylglycine and glutathione in women undergoing IVF.

Results

In blood plasma, the homocysteine, cysteine, and cysteinylglycine concentrations decreased significantly during stimulation with rec FSH (p < 0.001). We found significant differences in concentrations of cysteine and glutathione between follicles with or without retrieved oocytes. High intraindividual variability in concentrations of thiols was determined.

Conclusions

The concentration variability of thiols between single follicles is very high and we recommend mean at least from 3 follicles with/or without oocytes for characterization of each woman. It is the best to examine individual follicles for further research and analysis of fertility outcomes.

Background

Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that would benefit from ECLS. We aim to perform a prospective randomized study comparing prehospital intraarrest hypothermia combined with mechanical chest compression device, intrahospital ECLS and early invasive investigation and treatment in all patients with OHCA of presumed cardiac origin compared to a standard of care.

Methods

This paper describes methodology and design of the proposed trial. Patients with witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service (EMS) team and after performance of all initial procedures (defibrillation, airway management, intravenous access establishment) will be randomized to standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression device together with intranasal evaporative cooling will be instituted and patients will be transferred directly to cardiac center under ongoing CPR (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion criteria will be evaluated and if achieved, veno-arterial ECLS will be started. Invasive investigation and standard post resuscitation care will follow. Patients in standard arm will be managed on scene. When ROSC achieved, they will be transferred to cardiac center and further treated as per recent guidelines.

Primary outcome

6 months survival with good neurological outcome (Cerebral Performance Category 1–2). Secondary outcomes will include 30 day neurological and cardiac recovery.

Discussion

Authors introduce and offer a protocol of a proposed randomized study comparing a combined “hyperinvasive approach” to a standard of care in refractory OHCA. The protocol is opened for sharing by other cardiac centers with available ECLS and cathlab teams trained to admit patients with refractory cardiac arrest under ongoing CPR. A prove of concept study will be started soon. The aim of the authors is to establish a net of centers for a multicenter trial initiation in future.

Ethics and registration

The protocol has been approved by an Institutional Review Board, will be supported by a research grant from Internal Grant Agency of the Ministry of Health, Czech Republic NT 13225-4/2012 and has been registered under ClinicalTrials.gov identifier: NCT01511666.

Background

Older age, as a factor we cannot affect, is consistently one of the main negative prognostic values in patients with acute myocardial infarction. One of the most powerful factors that improves outcomes in patients with acute coronary syndromes is the revascularization preferably performed by percutaneous coronary intervention. No data is currently available for the role of age in large groups of consecutive patients with PCI as the nearly sole method of revascularization in AMI patients. The aim of this study was to analyze age-related differences in treatment strategies, results of PCI procedures and both in-hospital and long-term outcomes of consecutive patients with acute myocardial infarction.

Methods

Retrospective multicenter analysis of 3814 consecutive acute myocardial infarction patients divided into two groups according to age (1800 patients ≤ 65 years and 2014 patients > 65 years). Significantly more older patients had a history of diabetes mellitus and previous myocardial infarctions.

Results

The older population had a significantly lower rate of coronary angiographies (1726; 95.9% vs. 1860; 92.4%, p < 0.0001), PCI (1541; 85.6% vs. 1505; 74.7%, p < 0.001), achievement of optimal final TIMI flow 3 (1434; 79.7% vs. 1343; 66.7%, p < 0.001) and higher rate of unsuccessful reperfusion with final TIMI flow 0-1 (46; 2.6% vs. 78; 3.9%, p = 0.022). A total of 217 patients (5.7%) died during hospitalization, significantly more often in the older population (46; 2.6% vs. 171; 8.5%, p < 0.001). The long-term mortality (data for 2847 patients from 2 centers) was higher in the older population as well (5 years survival: 86.1% vs. 59.8%). Though not significantly different and in contrast with PCI, the presence of diabetes mellitus, previous MI, final TIMI flow and LAD, as the infarct-related artery, had relatively lower impact on the older patients. Severe heart failure on admission (Killip III-IV) was associated with the worst prognosis in the whole group of patients, though its significance was higher in the youngers (HR 6.04 vs. 3.14, p = 0.051 for Killip III and 12.24 vs. 5.65, p = 0.030 for Killip IV). We clearly demonstrated age as a strong discriminator for the whole population of AMI patients.

Conclusions

In a consecutive AMI population, the older group (>65 years) was associated with a less pronounced impact of risk factors on long-term outcome. To ascertain the coronary anatomy by coronary angiography and proceed to PCI if suitable regardless of age is crucial in all patients, though the primary success rate of PCI in the older age is lower. Age, when viewed as a risk factor, was a dominant discriminating factor in all patients.

Introduction

The prognosis of patients hospitalized with acute heart failure (AHF) is poor and risk stratification may help clinicians guide care. The objectives of the Acute Heart Failure Database (AHEAD) registry are to assess patient characteristics, etiology, treatment and outcome of AHF.

Methods

The AHEAD main registry includes patients hospitalized for AHF in seven centers with a Catheterization Laboratory Service in the Czech Republic. The data were collected from September 2006 to October 2009. The inclusion criteria for the database adhere to the European guidelines for AHF (2005) and patients were systematically classified according to the basic syndromes, type and etiology of AHF.

Results

Of 4,153 patients, 12.7% died during hospitalization. The median length of hospitalization was 7.1 days. Mean age of patients was 71.5 ± 12.4 years; men were younger (68.6 ± 12.4 years) compared to women (75.5 ± 11.5 years) (P < 0.001). De-novo heart failure was seen in 58.3% of the patients. According to the classification of heart failure syndromes, acute decompensated heart failure (ADHF) was reported in 55.3%, hypertensive AHF in 4.4%, pulmonary edema in 18.4%, cardiogenic shock in 14.7%, high output failure in 3.3%, and right heart failure in 3.8%. The mortality of cardiogenic shock was 62.7%, of right AHF 16.7%, of pulmonary edema 7.1%, of high output HF 6.1%, whereas the mortality of hypertensive AHF or ADHF was < 2.5%. According to multivariate analyses, low systolic blood pressure, low cholesterol level, hyponatremia, hyperkalemia, the use of inotropic agents and norepinephrine were predictive parameters for in-hospital mortality in patients without cardiogenic shock. Severe left ventricular dysfunction and renal insufficiency were predictive parameters for mortality in patients with cardiogenic shock. Invasive ventilation and age over 70 years were the most important predictive factors for mortality in both genders with or without cardiogenic shock.

Conclusions

The AHEAD Main registry provides up-to-date information on the etiology, treatment and hospital outcomes of patients hospitalized with AHF. The results highlight the highest risk patients.

Background

The initial pharmacokinetic study of a new anticancer agent (OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloroplatinum (IV) (LA-12) was complemented by proteomic screening of rat plasma. The objective of the study was to identify new LA-12 target proteins that serve as markers of LA-12 treatment, response and therapy monitoring.

Methods

Proteomic profiles were measured by surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) in 72 samples of rat plasma randomized according to LA-12 dose and time from administration. Correlation of 92 peak clusters with platinum concentration was evaluated using Spearman correlation analysis.

Results

We identified Retinol-binding protein 4 (RBP4) whose level correlated with LA-12 level in treated rats. Similar results were observed in randomly selected patients involved in Phase I clinical trials.

Conclusions

RBP4 induction is in agreement with known RBP4 regulation by amantadine and cisplatin. Since retinol metabolism is disrupted in many cancers and inversely associates with malignancy, these data identify a potential novel mechanism for the action of LA-12 and other similar anti-cancer drugs.

Background

We evaluated the associations among angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) early after presentation with MI with ST-segment elevation (STEMI).

Methods

A total of 556 patients with STEMI treated by primary PCI (421 patients without AHF and 135 patients with AHF) were the study population. The activity of BNP, NT-ProBNP and ACE were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI.

Results

In comparison with the II genotypes group, the DD/ID group had a higher level of ACE activity upon hospital admission (p < 0.001). We found a significantly higher level of ACE activity in patients with moderate LV dysfunction (EF 40-54%) in comparison both with patients with preserved LV function (EF ≥55%) and with patients with severe LV dysfunction (p = 0.028). A non-significant trend towards a higher incidence of mild AHF (22.1% vs. 16.02%, p = 0,093), a significantly higher value of end-systolic volume (ESV/BSA) (30.0 ± 12.3 vs. 28.5 ± 13.0; p < 0.05) and lower EF (50.2 ± 11.1 vs. 52.7 ± 11.7; p < 0.05) in the DD/ID genotypes group was noted. Even after multiple adjustments according to multivariate models, the EF for the DD/ID group remained significantly lower (p = 0,033). The DD/ID genotypes were associated with a significantly higher risk of EF <45% (OR 2.04 [95% CI 1.28; 3.25]).

Conclusions

These results suggest that the I/D polymorphism of ACE is associated with the development of LV dysfunction in the acute phase after STEMI. We demonstrated for the first time an association of the low ACE activity with the severe LV dysfunction, although patients with moderate LV dysfunction had higher level ACE activity than patients with preserved LV function.

AIM: To perform a comparative analysis of clinicopathological correlations of cyclooxygenase-2 (COX-2) expression in pancreatic cancer, examined by monoclonal and polyclonal antibodies.

METHODS: The COX-2 expression in 85 resection specimens of pancreatic ductal adenocarcinoma was immunohistochemically examined using both monoclonal and polyclonal antibodies. The final immunoscores were obtained by multiplying the percentage of positive cells with the numeric score reflecting the staining intensity. COX-2 expression levels were classified into three categories (0, 1+, and 2+) and the clinicopathological correlations were statistically evaluated and analyzed.

RESULTS: The positive tumor expression rates of COX-2 were 80.5% using monoclonal antibody and 69.4% using polyclonal antibody. In the Kaplan-Meier analysis, no significant correlations were found between levels of COX-2 expression and overall survival (OS), but trends to longer OS were found in COX-2 negative cases using monoclonal antibody. Significantly longer disease free survival was revealed in COX-2 negative cases using monoclonal antibody (P = 0.019). No correlations between COX-2 expression levels and grade (G), tumor (T) status and nodal (N) status were demonstrated. Low histological grade showed a strong association with a longer OS (P < 0.001). Correlation of survival and T status revealed a shorter OS in T3 tumors, but the results reached only marginal statistical significance (P = 0.070). In the multivariate Cox proportional hazards regression model, histological grade, T and N status remained valuable predictors of a worse survival with borderline significance for T [hazards ratio (HR) = 4.18 for G (if G = 3, P < 0.001); HR = 1.64 for T (if T = 3, P = 0.065); HR = 2.53 for N (if N = 1, P = 0.006)]. Higher grade, T or N status was associated with a worse OS.

CONCLUSION: The immunohistochemically assessed level of COX-2 expression does not seem to represent a valuable independent prognostic factor and is not superior to the conventional prognostic factors.