Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

Prognostic performance of critical care scores in patients undergoing transcatheter aortic valve implantation

Background: Critical care management of patients undergoing transcatheter aortic valve implantation (TAVI) is a major determinant of their outcome. Aims: The aim of this study was to compare the prognostic performance of four general scoring systems [Acute Physiology and Chronic Health Evaluation (APACHE), Simplified Acute Physiology Score (SAPS), Sequential Organ Failure Assessment (SOFA), and MultiOrgan Dysfunction (MOD) scores] in TAVI patients. Methods: Between 1 June 2008 and 30 June 2014, 75 patients (81.2 ± 6.4 years old, 36 men and 39 women) who underwent TAVI were scored during the first 24 h of their stay at the intensive care unit (ICU). The outcome measures were in-hospital and 30-day mortality and in-hospital and 30-day morbidity defined as myocardial infarction, implantation of permanent pacemaker, stroke, tamponade, major bleeding, vascular access site complications and prolonged ventilation. Results: Four patients (5.3%) died in ICU and one more during follow-up, indicating a 30-day mortality rate of 6.6%. Regarding in-hospital mortality, the area under the ROC curve (AUC) was 0.92 for SAPS II, 0.88 for APACHE II, 0.73 for MODS and 0.74 for SOFA. Regarding 30 day-mortality, SAPS II and APACHE II performed equally higher (AUC = 0.88) than the other two scores (0.79 for MODS and 0.80 for SOFA). SAPS II had the best calibration among all four scores for in-hospital and 30-day mortality (χ2= 3.06 and χ2= 3.29, respectively). AUCs for in-hospital and 30-day morbidity were above 0.7 for SAPS II and APACHE II. Conclusions: SAPS II and APACHE II are reliable mortality and morbidity risk stratification models for TAVI patients with high calibration and discrimination. © 2016, © The Intensive Care Society 2016

High neutrophil to lymphocyte ratio in type A acute aortic dissection facilitates diagnosis and predicts worse outcome

Objective: The authors investigated whether neutrophil to lymphocyte ratio (N/L) can contribute to the diagnosis and risk assessment in patients with type A acute aortic dissection (AAD). Methods: The authors studied 120 consecutive patients with type A AAD (group I) and compared them with 121 consecutive patients with chronic aneurysms (group II) and 121 age- and sex-matched healthy subjects (group III). Result: It was found that white blood cell count, N/L, D-dimer and C-reactive protein were significantly higher in group I versus both groups II and III (p < 0.001 for all comparisons). White blood cell count and D-dimer were much higher in patients who died compared to survivors in group I (p = 0.023 and p = 0.033, respectively). A cutoff value of N/L >4.6 was associated with 0.89 sensitivity and 0.91 specificity for AAD. Conclusion: High N/L may contribute to the diagnostic evaluation and prompt immediate therapy in patients with type A AAD. © 2015 Informa UK, Ltd