Effect of Statins on Platelet Activation and Function: From Molecular Pathways to Clinical Effects.

PURPOSE: Statins are a class of drugs widely used in clinical practice for their lipid-lowering and pleiotropic effects. In recent years, a correlation between statins and platelet function has been unveiled in the literature that might introduce new therapeutic indications for this class of drugs. This review is aimed at summarizing the mechanisms underlying statin-platelet interaction in the cardiologic scenario and building the basis for future in-depth studies. METHODS: We conducted a literature search through PubMed, Embase, EBSCO, Cochrane Database of Systematic Reviews, and Web of Science from their inception to June 2020. RESULTS: Many pathways could explain the interaction between statins and platelets, but the specific effect depends on the specific compound. Some could be mediated by enzymes that allow the entry of drugs into the cell (OATP2B1) and others by enzymes that mediate their activation (PLA2, MAPK, TAX2, PPARs, AKT, and COX-1), recruitment and adhesion (LOX-1, CD36, and CD40L), or apoptosis (BCL2). Statins also appear to have a synergistic effect with aspirin and low molecular weight heparins. Surprisingly, they seem to have an antagonistic effect with clopidogrel. CONCLUSION: There are many pathways potentially responsible for the interactions between statins and platelets. Their effect appears to be closely related, and each single effect can be barely measured. Also, the same compound might have complex downstream signaling with potentially opposite effects, i.e., beneficial or deleterious. The multiple clinical implications that can be derived as a result of this interaction, however, represent an excellent reason to develop future in-depth studies.

Statin treatment and hypertrophic scarring after cardiac surgery.

Wound healing process after surgical procedure plays a crucial role to prevent blood loss and infections. Hypertrophic scars might occur after surgery and are generally associated with an inflammatory burden. Cardiac surgery is intrinsically related to a strong systemic inflammatory state that might favor hypertrophic scarring. Besides lipid-lowering effects, statins are known for their pleiotropic and anti-inflammatory activity. The aim of this study was to investigate the impact of statins in the healing process after median sternotomy in patients undergoing cardiac surgery. All patients undergoing major cardiac surgery with median sternotomy and cardiopulmonary bypass, and subsequently evaluated in the outpatient clinic after discharge, were included in this study. A total of 930 Caucasian patients were retrospectively reviewed. At outpatient visit, 276 patients (29.7%) showed the formation of hypertrophic scars. Patients with hypertrophic scars tended to be younger (P = .001) and nonstatin users (P = .001). Logistic regression analysis confirmed the protective role of statins (odds ratio 0.39, 95% confidence interval 0.29-0.53, P = .001), after adjustment for age. A dose-dependent effect was confirmed, showing a more intensive protective effect for higher doses of statins. Statin use might be correlated with reduced hypertrophic scars after cardiac surgery through median sternotomy. A dose-dependent effect has been shown, and statin effect seems to be independent of age in a selected population undergoing surgery with an elevated inflammatory burden. Although further studies are warranted to elucidate the biologic mechanisms, the concept of using statins as anti-scarring agents is novel and should be investigated with tailored studies.

Deep Sternal Wound Infection (DSWI) and Mediastinitis After Cardiac Surgery: Current Approaches and Future Trends in Prevention and Management.

Median sternotomy is the most common access for cardiac surgery. Deep surgical wound infection (DSWI) and mediastinitis after median sternotomy remain significant clinical problems after cardiac surgery in terms of mortality, morbidity and healthcare-associated costs. Despite recent advances in medical management and consensus papers, their incidence ranges from 1% to 5%, and the associated mortality ranges from 20% to 50%. Recent studies in this field are providing excellent outcomes with promising results for the near future. The choice of sternal closure technique plays a crucial role in the prevention of DSWI and mediastinitis and should be tailored to the patient's characteristics, as clinical judgement and experience play a pivotal role. Early aggressive surgical debridement, vacuum-assisted closure (VAC) therapy, muscle flap and newer technologies are revolutionizing the paradigm of treatment of DSWI. Also, recent advances in tissue engineering have been refining potential approaches to tissue regeneration or substitution for enhanced wound repair. This editorial aims to briefly summarize the current and future techniques in DSWI prevention and treatment after cardiac surgery.

Guidelines on prosthetic heart valve management in infective endocarditis: a narrative review comparing American Heart Association/American College of Cardiology and European Society of Cardiology guidelines.

Infective endocarditis (IE) represented over the last year a growing medical and surgical concern. The changes in etiology and demographic of the disease, which now includes also a large proportion of iatrogenic conditions, has prompted new studies and updates in the guideline for IE treatment. The increasing use of intravascular and intracardiac devices has introduced new challenges in terms of both antibiotic resistance and surgical treatment of prosthetic endocarditis. Also, patients with complex congenital heart diseases, intravenous drug abusers and patients with chronic renal failure under hemodialysis have been added to the list of high-risk subjects for IE. Important aspects concerning the establishment of the endocarditis team, the clinical management, the optimal medical therapy and the indication and timing for surgery are arguments of debate and controversy across the literature. In particular, the most adequate strategy to be adopted in the context of concomitant neurological complication remains greatly debated. Despite attempts to standardize the practice in IE, the lack of powered randomized clinical evidence prevented the achievement of a univocal consensus in several aspects of the management of IE. This situation reflects in some differences in the recommendation promoted by the European Society of Cardiology and American Heart Association/American College of Cardiology. In this review, we will compare the European Society of Cardiology and the American Heart Association guidelines and discuss important aspects related to clinical management and indications of for treatment.

Sternal wound closure in the current era: the need of a tailored approach.

OBJECTIVE: Median sternotomy remains the most common access to perform cardiac surgery procedures. However, the experience of the operating surgeon remains a crucial factor during sternal closure to avoid potential complications related to poor sternal healing, such as mediastinitis. Considering the lack of major randomized controlled trials and the heterogeneity of the current literature, this narrative review aims to summarize the different techniques and approaches to sternal closure with the aim to investigate their reflections into clinical outcomes and to inform the choice on the most effective closure method after median sternotomy. METHODS: A literature search through PubMed, Embase, EBSCO, Cochrane database of systematic reviews, and Web of Science from its inception up to April 2019 using the following search keywords in various combinations: sternal, sternotomy, mediastinitis, deep sternal wound infection, cardiac surgery, closure. RESULTS: Single wire fixation methods, at present, seems the most useful method to perform sternal closure in routine patients, although patients with a fragile sternum might benefit more from a figure-of-eight technique. In high-risk patients (e.g. chronic pulmonary disease, obesity, bilateral internal mammary artery harvesting, diabetes, off-midline sternotomy), rigid plate fixation is currently the most effective method, if available; alternatively, weave techniques could be used. CONCLUSION: The choice among the sternal closure techniques should be mainly inspired and tailored on the patient's characteristics, and correct judgement and experience play a pivotal role. A decisional algorithm has been proposed as an attempt to overcome the absence of specific guidelines and to guide the operative approach. This operative approach might be used also in non-cardiac procedure in which median sternotomy is required, such as in case of thoracic surgery.

Impact of Ethnicity on the Prevalence of Early Repolarization Pattern in Children: Comparison Between Caucasian and African Populations.

The patterns and prevalence of early repolarization pattern (ER) in pediatric populations from ethnic backgrounds other than Caucasian have not been determined. Black African children (ages 4-12) from north-west Madagascar were prospectively recruited and their ECGs compared with those of age- and sex-matched Caucasian ethnicity individuals. ER was defined by ≥ 0.1 mV J-point elevation in at least two contiguous inferior and/or lateral ECG leads. A total of 616 children were included. There was a trend toward a higher frequency of ER in the Africans compared to the Caucasians (23.3% vs. 17.1%, respectively, p = 0.053). The subtype (slurred vs. notched) and location of ER (lateral, inferior, or inferior-lateral) were significantly different in the two groups (p < 0.001 and p = 0.020, respectively). There was no significant difference in the number of high-risk ECG features of ERP (i.e., horizontal/descendent pattern, inferior or inferior-lateral location or J-waves ≥ 2 mm) between African and Caucasian children. On the multivariate analysis, African ethnicity was an independent predictive factor of ER (OR 3.57, 95% CI 2.04-6.25, p < 0.001). African children have an increased risk of ER compared to Caucasian counterparts. Future studies should clarify the clinical and prognostic significance of ER in the pediatric population, and whether ethnicity has an impact on the outcomes.

Inflammatory Response and Endothelial Dysfunction Following Cardiopulmonary Bypass: Pathophysiology and Pharmacological Targets.

BACKGROUND: Endothelial injury occurring during cardiopulmonary bypass is a major contributing factor in the development of organ dysfunction, which leads to many of the postoperative complications occurring during cardiac surgery. OBJECTIVE: This narrative review aims to summarize the main mechanisms of cardiopulmonary bypass - related disease, evaluating the unfavorable events leading to tissue injury, with a description of current pharmacologic and non-pharmacologic mechanisms to reduce CPB-related injury. METHODS: A Medline/Pubmed/Scopus search was conducted using clinical queries with the key terms "cardiac surgery", "cardiopulmonary bypass", "inflammation" and "endothelial injury", and related MeSH terms, until July 2019. The search strategy included meta-analyses, randomized controlled trials, clinical trials, reviews and pertinent references. Patents were searched using the same key terms from https://patents.google.com/, www.uspto.gov, and www.freepatentsonline.com. RESULTS: In this review, we discuss the current knowledge of the mechanisms of vascular endothelial cell injury, the acute inflammatory response, and the regulatory factors that control the extent of vascular injury during extracorporeal circulation, summarizing the main target of anti-inflammatory pharmacologic and non-pharmacologic strategies. CONCLUSION: Inflammatory response and endothelial dysfunction following cardiopulmonary bypass are the prices to pay for the benefits offered during cardiac surgery procedures. Counteracting the detrimental effect of extracorporeal circulation appears to be crucial to improve clinical outcomes in pediatric and adult cardiac surgery. The intrinsic complexity and the tight interplay of the factors involved might require a holistic approach against inflammation and endothelial response.

Preoperative atorvastatin reduces bleeding and blood transfusions in patients undergoing elective isolated aortic valve replacement.

OBJECTIVES: Minimization of bleeding to reduce the use of blood products is of utmost importance in cardiac surgery. Statins are known for their pleiotropic effects beyond lipid-lowering properties, and the use of atorvastatin preoperatively is associated with reduced risk of bleeding and blood product use after coronary surgery. However, no studies have investigated if this beneficial effect also extends to aortic valve surgery. METHODS: In this retrospective cohort study, 1145 consecutive patients undergoing elective primary isolated aortic valve replacement meeting the inclusion and exclusion criteria were selected from January 2009 to December 2017 (547 in the atorvastatin group, 598 in the control group). Postoperative bleeding, blood product use, and complications were monitored during hospitalization. RESULTS: Postoperative bleeding was significantly lower in the atorvastatin group compared with the controls in the first 12 h after surgery (372 ± 137 vs 561 ± 219 ml; P = 0.001) and considering overall bleeding (678 ± 387 vs 981 ± 345 ml, P = 0.001). A total of 32.3% of controls and 26.3% of atorvastatin users received packed red blood cells (P = 0.027), and major surgical complications were similar between the groups. Postoperative length of stay was shorter in the atorvastatin group with an average reduction of 1 day of hospitalization (6.0 ± 1.4 vs 6.9 ± 2.1 days; P = 0.001). Postoperative bleeding among the atorvastatin-treated patients was significantly greater in those taking lower doses compared to those taking higher doses of atorvastatin with a 20% between-group difference (P = 0.001). CONCLUSIONS: Preoperative treatment with atorvastatin might reduce postoperative bleeding and transfusion of packed red blood cells in patients undergoing elective isolated aortic valve replacement. This result might translate into faster recovery after surgery and reduced hospitalization costs.

ECG is an inefficient screening-tool for left ventricular hypertrophy in normotensive African children population.

BACKGROUND: Left ventricular hypertrophy (LVH) is a marker of pediatric hypertension and predicts development of cardiovascular events. Electrocardiography (ECG) screening is used in pediatrics to detect LVH thanks to major accessibility, reproducibility and easy to use compared to transthoracic echocardiography (TTE), that remains the standard technique. Several diseases were previously investigated, but no data exists regarding our study population. The aim of our study was to evaluate the relationship between electrocardiographic and echocardiographic criteria of LVH in normotensive African children. METHODS: We studied 313 children (mean age 7,8 ± 3 yo), in north-Madagascar. They underwent ECG and TTE. Sokolow-Lyon index was calculated to identify ECG-LVH (>35 mm). Left ventricle mass (LVM) with TTE was calculated and indexed by height(2.7) (LVMI(2.7)) and weight (LVMI(w)). We report the prevalence of TTE-LVH using three methods: (1) calculating percentiles age- and sex- specific with values >95th percentile identifying LVH; (2) LVMI(2.7) >51 g/m(2.7); (3) LVMI(w) >3.4 g/weight. RESULTS: 40 (13%) children showed LVMI values >95th percentile, 24 children (8%) an LVMI(2.7) >51 g/m(2.7) while 19 children (6%) an LVMI(w) >3.4 g/kg. LVH-ECG by Sokolow-Lyon index was present in five, three and three children respectively, with poor values of sensitivity (ranging from 13 to 16%), positive predictive value (from 11 to 18%) and high values of specificity (up to 92%). The effects of anthropometrics parameters on Sokolow-Lyon were analyzed and showed poor correlation. CONCLUSION: ECG is a poor screening test for detecting LVH in children. In clinical practice, TTE remains the only tool to be used to exclude LVH.

Effects of Malnutrition on Left Ventricular Mass in a North-Malagasy Children Population.

BACKGROUND: Malnutrition among children population of less developed countries is a major health problem. Inadequate food intake and infectious diseases are combined to increase further the prevalence. Malnourishment brings to muscle cells loss with development of cardiac complications, like arrhythmias, cardiomyopathy and sudden death. In developed countries, malnutrition has generally a different etiology, like chronic diseases. The aim of our study was to investigate the correlation between malnutrition and left ventricular mass in an African children population. METHODS: 313 children were studied, in the region of Antsiranana, Madagascar, with age ranging from 4 to 16 years old (mean 7,8 ± 3 years). A clinical and echocardiographic evaluation was performed with annotation of anthropometric and left ventricle parameters. Malnutrition was defined as a body mass index (BMI) value age- and sex-specific of 16, 17 and 18,5 at the age of 18, or under the 15th percentile. Left ventricle mass was indexed by height2.7 (LVMI). RESULTS: We identified a very high prevalence of children malnutrition: 124 children, according to BMI values, and 100 children under the 15th percentile. LVMI values have shown to be increased in proportion to BMI percentiles ranging from 29,8 ± 10,8 g/m2.7 in the malnutrition group to 45 ± 15,1 g/m2.7 in >95th percentile group. LVMI values in children < 15th BMI percentile were significantly lower compared to normal nutritional status (29,8 ± 10,8 g/m2,7 vs. 32,9 ± 12,1 g/m2,7, p = 0.02). Also with BMI values evaluation, malnourished children showed statistically lower values of LVMI (29,3 ± 10,1 g/m2,7 vs. 33,6 ± 12,5 g/m2,7, p = 0.001). CONCLUSION: In African children population, the malnourishment status is correlated with cardiac muscle mass decrease, which appears to be reduced in proportion to the decrease in body size.