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

Platelet to lymphocyte ratio in acute aortic dissection

Background: Inflammation plays an important role in the initiation and progression of acute aortic dissection (AAD). New inflammatory indices derived from full cell blood count and its differential may be associated with increased risk. We evaluated platelet-lymphocyte (PLR), red cell distribution width (RDW) and RDW/PLT's (platelets) (RPR) in AAD. Methods: We studied 120 consecutive patients with AAD type I admitted for emergency surgery (group I), 121 consecutive patients with aortic aneurysms of the ascending aorta prior to elective repair (group II) and 121 controls (group III), age and sex matched. Results: PLR was significantly higher in group I vs both groups II and III (P <.001). There was an excellent correlation of PLR with neutrophil/lymphocyte ratio (NLR) in all three groups (P <.001 for all). After adjustment for hemoglobin, RDW did not differ but RPR remained significantly higher in group I compared to groups II and III (P <.001). The best cutoff value of PLR to predict dissection was 159 with 53% sensitivity and 86% specificity. No association between PLR, RDW, and RPR and mortality in group I was found. Conclusions: Indices derived from full cell blood count may provide diagnostic information in patients with AAD; whether these indices may contribute to prognosis assessment should be further investigated. © 2018 Wiley Periodicals, Inc

Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5 ± 10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7 ± 9.2 % and low logistic EuroScore (3.5 ± 3.2 %) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11-24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p = 0.007 ]. OPN levels were positively related to EuroScore (r = 0.2, p = 0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p = 0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43-4.99), p = 0.527 ]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p = 0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome. © 2016 Eftihia Sbarouni et al

High homocysteine and low folate concentrations in acute aortic dissection

Background: Biomarkers for monitoring progression and prognosis of thoracic aneurysm are of great interest. Homocysteine (Hcy) induces elastolysis in arterial media and may directly affect fibrillin-1 or collagen whereas lipoprotein (Lp) (a) inhibits elastolysis by reducing activation of matrix metallopeptidase-9. Methods: We studied 31 consecutive patients with acute aortic dissection (AAD) admitted for emergency surgery (group I, 60 ± 13 years old, 25 men), 30 consecutive patients with chronic aneurysms of the ascending aorta (group II, 67 ± 12 years old, 24 men) and 20 healthy controls (group III, 58 ± 15 years old, 14 men). We evaluated Hcy, folate, B12, Lp(a) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism at baseline. Results: Hcy, folate and B12 differed significantly among the 3 studied groups (P = 0.016, P = 0.004 and P = 0.001, respectively). The levels of Hcy and B12 were significantly higher in group I compared to both groups II and III (P = 0.05 and P = 0.002, P < 0.001 and P = 0.017, respectively) and without significant differences between groups II and III (P = 0.083 and P = 0.124). Folate was significantly lower in group I compared to both groups II and III (P = 0.001 and P = 0.006, respectively) and without marked difference between groups II and III (P = 0.409). No significant difference was found in serum levels of Lp (a) (P = 0.074) or among the frequency of MTHFR C677T genotypes. Conclusions: Patients with AAD present with higher Hcy and lower folate compared to both chronic aneurysms and controls. © 2012 Elsevier Ireland Ltd. All rights reserved

Long-term quality of life improvement after transcatheter aortic valve implantation

Background: Transcatheter aortic valve implantation (TAVI) is a novel therapeutic option for severe aortic stenosis in old patients with high surgical risk. The aim of this study was to assess changes in quality of life (QoL) along with functional status and late survival after this procedure. Methods: Thirty-six consecutive patients (80.5 ± 5.9 years, 21 men and 15 women) with a logistic Euroscore of 29.7 ± 13.7 underwent TAVI using the 18-Fr CoreValve prosthesis. Aortic valve prosthesis was inserted retrograde using a femoral or a subclavian arterial approach. QoL was evaluated by administering the Short Form 36 (SF-36) tool and the shorter SF-12 version 2 (SF-12v2) questionnaires before and 1-year after TAVI. Results: TAVI was successfully performed in all patients. The estimated 1-year overall survival rate using Kaplan-Meier method was 68%. One-year follow-up also showed a marked improvement in echocardiographic parameters (peak gradient 76.2 ± 26.1 vs 15.4 ± 7.8 mm Hg, P <.001; aortic valve area 0.7 ± 0.1 vs 2.6 ± 2.7 cm2, P <.001) with a significant change in New York Heart Association class (3 ± 0.7 vs 1.2 ± 0.4, P <.001). Both preprocedural summary SF-36 and SF-12v12 physical and mental scores showed a significant improvement 1 year after TAVI (21.6 vs 46.7, P <.001; 42.9 vs 55.2, P <.001; 22 vs 48.9, P <.001; 43.3 vs 52.2, P <.001, respectively). Conclusions: Our results show a marked 1-year clinical benefit in functional status and physical and mental health in patients who underwent TAVI. © 2011 Mosby, Inc. All rights reserved