Impact of the Main Cardiovascular Risk Factors on Plasma Extracellular Vesicles and Their Influence on the Heart's Vulnerability to Ischemia-Reperfusion Injury.

The majority of cardiovascular deaths are associated with acute coronary syndrome, especially ST-elevation myocardial infarction. Therapeutic reperfusion alone can contribute up to 40 percent of total infarct size following coronary artery occlusion, which is called ischemia-reperfusion injury (IRI). Its size depends on many factors, including the main risk factors of cardiovascular mortality, such as age, sex, systolic blood pressure, smoking, and total cholesterol level as well as obesity, diabetes, and physical effort. Extracellular vesicles (EVs) are membrane-coated particles released by every type of cell, which can carry content that affects the functioning of other tissues. Their role is essential in the communication between healthy and dysfunctional cells. In this article, data on the variability of the content of EVs in patients with the most prevalent cardiovascular risk factors is presented, and their influence on IRI is discussed.

Associations Between Preoperative Glucose and Hemoglobin A1c Level and Myocardial Injury After Noncardiac Surgery.

Background Perioperative blood glucose level has shown an association with postoperative outcomes. We compared the incidences of myocardial injury after noncardiac surgery (MINS) and 30-day mortality, according to preoperative blood glucose and hemoglobin A1c (HbA1c) levels. Methods and Results The patients were divided according to blood glucose level within 1 day before surgery. The hyperglycemia group was defined with fasting glucose >140 mg/dL or random glucose >180 mg/dL. In addition, we compared the outcomes according to HbA1c >6.5% among patients with available HbA1c within 3 months before surgery. The primary outcome was MINS, and 30-day mortality was also compared. A total of 12 304 patients were enrolled and divided into 2 groups: 8324 (67.7%) in the normal group and 3980 (32.3%) in the hyperglycemia group. After adjustment with inverse probability of weighting, the hyperglycemia group exhibited significantly higher incidences of MINS and 30-day mortality (18.7% versus 27.6%; odds ratio, 1.29; 95% CI, 1.18-1.42; P<0.001; and 2.0% versus 5.1%; hazard ratio, 2.00; 95% CI, 1.61-2.49; P<0.001, respectively). In contrast to blood glucose, HbA1c was not associated with MINS or 30-day mortality. Conclusions Preoperative hyperglycemia was associated with MINS and 30-day mortality, whereas HbA1c was not. Immediate glucose control may be more crucial than long-term glucose control in patients undergoing noncardiac surgery. Registration URL: https://www.cris.nih.go.kr; Unique identifier: KCT0004244.

Sex-dependent effect of perinatal hypoxia on cardiac tolerance to oxygen deprivation in adults.

Epidemiological studies have demonstrated a relationship between the adverse influence of perinatal development and increased risk of ischemic heart disease in adults. From negative factors to which the fetus is subjected, the most important is hypoxia. The fetus may experience hypoxic stress under different conditions, including pregnancy at high altitude, pregnancy with anemia, placental insufficiency, and heart, lung, and kidney disease. One of the most common insults during the early stages of postnatal development is hypoxemia due to congenital cyanotic heart defects. Experimental studies have demonstrated a link between early hypoxia and increased risk of ischemia/reperfusion injury (I/R) in adults. Furthermore, it has been observed that late myocardial effects of chronic hypoxia, experienced in early life, may be sex-dependent. Unlike in males, perinatal hypoxia significantly increased cardiac tolerance to acute I/R injury in adult females, expressed as decreased infarct size and lower incidence of ischemic arrhythmias. It was suggested that early hypoxia may result in sex-dependent programming of specific genes in the offspring with the consequence of increased cardiac susceptibility to I/R injury in adult males. These results would have important clinical implications, since cardiac sensitivity to oxygen deprivation in adult patients may be significantly influenced by perinatal hypoxia in a sex-dependent manner.

The role of aldosterone inhibitors in cardiac ischemia-reperfusion injury.

Myocardial ischaemia-reperfusion (I/R) injury is a well-known term for exacerbation of cellular destruction and dysfunction after the restoration of blood flow to a previously ischaemic heart. A vast number of studies that have demonstrated that the role of mineralocorticoids in cardiovascular diseases is based on the use of pharmacological mineralocorticoid receptor (MR) antagonists. This review paper aimed to summarize current knowledge on the effects of MR antagonists on myocardial I/R injury as well as postinfarction remodeling. Animal models, predominantly the Langendorff technique and left anterior descending coronary artery occlusion, have confirmed the potency of MR antagonists as preconditioning and postconditioning agents in limiting infarct size and postinfarction remodeling. Several preclinical studies in rodents have established and proved possible mechanisms of cardioprotection by MR antagonists, such as reduction of oxidative stress, reduction of inflammation, and apoptosis, therefore limiting the infarct zone. However, the results of some clinical trials are inconsistent, since they reported no benefit of MR antagonists in acute myocardial infarction. Due to this, further studies and the results of ongoing clinical trials regarding MR antagonist administration in patients with acute myocardial infarction are being awaited with great interest.

Parameters predicting COVID-19-induced myocardial injury and mortality.

Clinical manifestations of COVID-19 affect many organs, including the heart. Cardiovascular disease is a dominant comorbidity and prognostic factors predicting risk for critical courses are highly needed. Moreover, immunomechanisms underlying COVID-induced myocardial damage are poorly understood. OBJECTIVE: To elucidate prognostic markers to identify patients at risk. RESULTS: Only patients with pericardial effusion (PE) developed a severe disease course, and those who died could be identified by a high CD8/Treg/monocyte ratio. Ten out of 19 COVID-19 patients presented with PE, 7 (78%) of these had elevated APACHE-II mortality risk-score, requiring mechanical ventilation. At admission, PE patients showed signs of systemic and cardiac inflammation in NMR and impaired cardiac function as detected by transthoracic echocardiography (TTE), whereas parameters of myocardial injury e.g. high sensitive troponin-t (hs-TnT) were not yet increased. During the course of disease, hs-TnT rose in 8 of the PE-patients above 16 ng/l, 7 had to undergo ventilatory therapy and 4 of them died. FACS at admission showed in PE patients elevated frequencies of CD3+CD8+ T cells among all CD3+ T-cells, and lower frequencies of Tregs and CD14+HLA-DR+-monocytes. A high CD8/Treg/monocyte ratio predicted a severe disease course in PE patients, and was associated with high serum levels of antiviral cytokines. By contrast, patients without PE and PE patients with a low CD8/Treg/monocyte ratio neither had to be intubated, nor died. CONCLUSIONS: PE predicts cardiac injury in COVID-19 patients. Therefore, TTE should be performed at admission. Immunological parameters for dysfunctional antiviral immunity, such as the CD8/Treg/monocyte ratio used here, supports risk assessment by predicting poor prognosis.

Diabetic Cardiomyopathy and Ischemic Heart Disease: Prevention and Therapy by Exercise and Conditioning.

Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. In addition, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.

Proteinase­activated receptor 2 deficiency is a protective factor against cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury.

Previous studies have established that proteinase­â€‹activated receptor 2 (PAR2) activation protects against myocardial ischemia/reperfusion injury (MI/RI). However, the role of PAR2 deficiency in MI/RI remains unclear. The aim of the present study was to examine the effect of PAR2 deficiency on cardiomyocyte apoptosis and to clarify the potential molecular mechanisms for its protective effect against MI/RI. Using a mouse model of MI/RI, cardiac function was evaluated by echocardiography, infarct size was assessed by triphenyltetrazolium chloride staining, and myocardial cell apoptosis was measured by terminal deoxynucleotide transferase­mediated dUTP nick end­labeling staining. Annexin V/propidium iodide staining, and expression of Bcl­2 and cleaved PARP were determined to assess apoptosis in myocardial H9c2 cells exposed to hypoxia/reoxygenation (H/R) injury­simulating MI/RI. Phosphorylated ERK1/2, JNK, and p38 MAPK protein expression levels were analyzed by western blotting. The findings indicated that PAR2 deficiency markedly reduced cardiomyocyte apoptosis in the MI/RI mouse model, as well as in myocardial H9c2 cells exposed to H/R. Furthermore, PAR2 knockdown clearly prevented phosphorylation of ERK1/2 and JNK in myocardial H9c2 cells. The results revealed that PAR2 deficiency alleviated MI/RI­associated apoptosis by inhibiting phosphorylation of ERK1/2 and JNK. Therefore, targeted PAR2 silencing may be a potential therapeutic approach for alleviation of MI/RI.

Editor's Choice- Pathophysiology and therapy of myocardial ischaemia/reperfusion syndrome.

There is a need to find interventions able to reduce the extent of injury in reperfused ST-segment elevation myocardial infarction (STEMI) beyond timely reperfusion. In this review, we summarise the clinical impact of STEMI from epidemiological, clinical and biological perspectives. We also revise the pathophysiology underlying the ischaemia/reperfusion syndrome occurring in reperfused STEMI, including the several players involved in this syndrome, such as cardiomyocytes, microcirculation and circulating cells. Interventions aimed to reduce the resultant infarct size, known as cardioprotective therapies, are extensively discussed, putting the focus on both mechanical interventions (i.e. ischaemic conditioning) and promising pharmacological therapies, such as early intravenous metoprolol, exenatide and other glucose modulators, N-acetylcysteine as well as on some other classic therapies which have failed to be translated to the clinical arena. Novel targets for evolving therapeutic interventions to ameliorate ischaemia/reperfusion injury are also discussed. Finally, we highlight the necessity to improve the study design of future randomised clinical trials in the field, as well as to select patients better who can most likely benefit from cardioprotective interventions.

Blood cardioplegia benefits only patients with a long cross-clamp time.

INTRODUCTION: A clear advantage of blood versus crystalloid cardioplegia has not yet been observed in smaller population studies. The purpose of this article was to further investigate the clinical outcomes of blood versus crystalloid cardioplegia in a large propensity-matched cohort of patients who underwent cardiac surgery. METHODS: The study was a single-centre study. Data was withdrawn from the Western Denmark Heart Registry, which comprises a perfusion section for each procedure. A total of 4,852 patients were propensity matched into crystalloid (CC) vs blood cardioplegia (BC) groups. The primary end points were creatinine kinase-MB (CKMB) elevation, acute myocardial infarction (AMI), stroke, dialysis, coronary angiography (CAG) and mortality (30 days and 6 months). RESULTS: We found lower odds ratio in 30-day mortality in the BC group (OR 0.21; CI 0.06-0.68), but no difference in overall 6-month mortality. There was no difference in CKMB elevation, AMI, dialysis or stroke. Several end points were further analysed for different cross-clamp times. In the CC group, ventilation time above 600 minutes was seen more often in almost all cross-clamp time intervals (23.5 % vs 12.2 %; p<0.0001; χ2-test) and 6-month mortality was significantly higher when the cross-clamp time exceeded 210 minutes (64.3 vs 23.8; p=0.018; χ2-test). CONCLUSIONS: We did not find clear evidence of superiority of either type in the uncomplicated patient. When prolonged cross-clamp time or postoperative ventilation is expected, this study indicates that blood cardioplegia might be preferable.

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

BACKGROUND: Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC. METHODS AND RESULTS: In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively. CONCLUSIONS: Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703.

Effect of Remote Ischemic Preconditioning on Outcomes in Adult Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Studies.

BACKGROUND: Remote ischemic preconditioning (RIPC) has been demonstrated to prevent organ dysfunction in cardiac surgery patients. However, recent large, prospective, multicenter, randomized controlled trials (RCTs) had controversial results. Thus, a meta-analysis of RCTs was performed to investigate whether RIPC can reduce the incidence of acute myocardial infarction (AMI), acute kidney injury (AKI), and mortality in adult cardiac surgery patients. METHODS: Study data were collected from Medline, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. RCTs involving the effect of RIPC on organ protection in cardiac surgery patients, which reported the concentration or total release of creatine kinase-myocardial band, troponin I/troponin T (TNI/TNT) after operation, or the incidence of AMI, AKI, or mortality, were selected. Two reviewers independently extracted data using a standardized data extraction protocol where TNI or TNT concentrations; total TNI released after cardiac surgery; and the incidence of AKI, AMI, and mortality were recorded. Review Manager 5.3 software was used to analyze the data. RESULTS: Thirty trials, including 7036 patients were included in the analyses. RIPC significantly decreased the concentration of TNI/TNT (standard mean difference [SMD], -0.25 ng/mL; 95% confidence interval [CI], -0.41 to -0.048 ng/mL; P = .004), creatine kinase-myocardial band (SMD, -0.22; 95% CI, -0.07-0.35 ng/mL; P = .46), and the total TNI/TNT release (SMD, -0.49 ng/mL; 95% CI, -0.93 to -0.55 ng/mL; P = .03) in cardiac surgery patients after a procedure. However, RIPC could not reduce the incidence of AMI (relative risk, 0.89; 95% CI, 0.70-1.13; P = .34) and AKI (relative risk, 0.88; 95% CI, 0.72-1.06; P = .18), and there was also no effect of RIPC on mortality in adult cardiac surgery patients. Interestingly, subgroup analysis showed that RIPC reduced incidence of AKI and mortality of cardiac surgery patients who received volatile agent anesthesia. CONCLUSIONS: Our meta-analysis demonstrated that RIPC reduced TNI/TNT release after cardiac surgery. RIPC did not significantly reduce the incidence of AKI, AMI, and mortality. However, RIPC could reduce mortality in patients receiving volatile inhalational agent anesthesia.

Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.

BACKGROUND: On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. METHODS: We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia-reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia-reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901. FINDINGS: In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32-0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68-0·93; p=0·0045]). Ex-vivo analysis of human myocardium revealed an intrinsic morning-afternoon variation in hypoxia-reoxygenation tolerance, concomitant with transcriptional alterations in circadian gene expression with the nuclear receptor Rev-Erbα being highest in the morning. In a mouse Langendorff model of hypoxia-reoxygenation myocardial injury, Rev-Erbα gene deletion or antagonist treatment reduced injury at the time of sleep-to-wake transition, through an increase in the expression of the ischaemia-reperfusion injury modulator CDKN1a/p21. INTERPRETATION: Perioperative myocardial injury is transcriptionally orchestrated by the circadian clock in patients undergoing aortic valve replacement, and Rev-Erbα antagonism seems to be a pharmacological strategy for cardioprotection. Afternoon surgery might provide perioperative myocardial protection and lead to improved patient outcomes compared with morning surgery. FUNDING: Fondation de France, Fédération Française de Cardiologie, EU-FP7-Eurhythdia, Agence Nationale pour la Recherche ANR-10-LABX-46, and CPER-Centre Transdisciplinaire de Recherche sur la Longévité.

Review of a causal role of fructose-containing sugars in myocardial susceptibility to ischemia/reperfusion injury.

In 2012, the World Health Organization Global Status Report on noncommunicable diseases showed that 7.4 million deaths were due to ischemic heart disease. Consequently, cardiovascular disease is a significant health burden, especially when partnered with comorbidities such as obesity, metabolic syndrome, and type 2 diabetes mellitus. Of note, these diseases can all be induced or exacerbated by diet. Carbohydrates, in particular, fructose and glucose, generally form the largest part of the human diet. Accumulating evidence from animal studies suggests that if large amounts of fructose are consumed either in isolation or in combination with glucose (fructose-containing sugars), myocardial susceptibility to ischemia/reperfusion (I/R) injury increases. However, the underlying mechanisms that predisposes the myocardium to I/R injury in the fructose model are not elucidated, and no single mechanistic pathway has been described. Based on all available data on this topic, this review describes previously investigated mechanisms and highlights 3 main mechanistic pathways whereby fructose has shown to increase myocardial susceptibility to I/R injury. These pathways include (1) increased reactive oxygen species, resulting in reduced nitric oxide synthase and coronary flow; (2) elevated plasma fatty acids and insulin, leading to increased cardiac triglyceride content and lipotoxicity; and (3) disrupted myocardial calcium handling/homeostasis. Moreover, we highlight various factors that should be taken into account when the fructose animal model is used, such as rat strain, treatment periods, and doses. We argue that failure to do so would result in erratic inferences drawn from the existing body of evidence on fructose animal models.

Effects of prostaglandin E1 on reperfusion injury patients: A meta-analysis of randomized controlled trials.

BACKGROUND: Prostaglandin E1 (PGE1) is widely used as a pretreatment for myocardial reperfusion injury in animal experiments. However, the cardioprotective effects of PGE1 in patients have not been established. We performed a meta-analysis to investigate whether PGE1 is cardioprotective, based on the reduction of correlative reperfusion injury events (CRIE), major adverse cardiac events (MACE), and biomarker release in patients with ischemia reperfusion injury. METHODS: The Medline, EMBASE, and Cochrane databases were searched for randomized clinical trials confirming the effects of PGE1. Two investigators independently selected suitable trials, assessed trial quality, and extracted data. RESULTS: Six studies in patients undergoing percutaneous coronary intervention (4 studies) and cardiac surgery (2 studies), comprising a total of 445 patients, were included in this review. The results showed that PGE1 reduced the incidence of CRIE (relative ratio 0.4 [95% confidence interval 0.43, 0.95]), the incidence of MACE (0.35 [0.17, 0.70]), and the level of troponin T (standardized mean difference 20.28 [20.47, 20.09]), creatine kinase-MB (-1.74 [-3.21, - 0.27]), interleukin-6 (-1.37 [-2.69, - 0.04]), and interleukin-8 (-2.05 [-2.75, - 1.34]). CONCLUSION: PGE1 may have beneficial effects on myocardial reperfusion injury in the clinic.

A longer total duration of rapid ventricular pacing does not increase the risk of postprocedural myocardial injury in patients who undergo transcatheter aortic valve implantation.

Rapid ventricular pacing (RVP) is used during transcatheter aortic valve implantation (TAVI). RVP disturbs myocardial oxygen balance, and when prolonged, it may cause procedure-related myocardial injury (PMI). This study investigated whether a longer duration of RVP increased the occurrence of PMI or worsened long-term mortality after TAVI. We retrospectively analyzed data from 188 patients who underwent TAVI in our institute from January 2013 to July 2015. Myocardial injury was represented by the peak value of creatine kinase-myocardial band (CK-MB) within 72 h after the procedure; an increase greater than 5 times the upper reference limit was regarded as PMI. There was no difference in RVP time (RVPT) between patients with and without PMI (median [range]: 57 [9-189] s vs. 54 [0-159] s, p = 0.9). A higher peak CK-MB was significantly correlated with the apical approach for the procedure (p < 0.001) but not with total RVPT (p = 0.22). A subanalysis of 133 patients whose troponin I was tested within 72 h postprocedurally showed no correlation between the peak value and RVPT (p = 0.40). Shortening RVPT did not result in myocardial protection; thus, RVPT during TAVI should be sufficient to optimize valve placement.

Clinic Predictive Factors for Insufficient Myocardial Reperfusion in ST-Segment Elevation Myocardial Infarction Patients Treated with Selective Aspiration Thrombectomy during Primary Percutaneous Coronary Intervention.

Background. Insufficient data are available on the potential benefit of selective aspiration and clinical predictors for no-reflow in STEMI patients undergoing primary percutaneous coronary intervention (PPCI) adjunct with aspiration thrombectomy. Objective. The aim of our study was to investigate clinical predictors for insufficient reperfusion in patients with high thrombus burden treated with PPCI and manual aspiration thrombectomy. Methods. From January 2011 till December 2015, 277 STEMI patients undergoing manual aspiration thrombectomy and PPCI were selected and 202 patients with a Thrombolysis in Myocardial Infarction (TIMI) thrombus grade 4~5 were eventually involved in our study. According to a cTFC value, patients were divided into Group I (cTFC > 40), namely, insufficient reperfusion group; Group II (cTFC ≤ 40), namely, sufficient reperfusion group. Results. Univariate analysis showed that hypertension, multivessel disease, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were negative predictors for insufficient reperfusion. After multivariate adjustment, age ≧ 60 years, hypertension, time from symptom to PCI (≧4.8 hours), and postaspiration cTFC > 40 were independently associated with insufficient reperfusion in STEMI patients treated with manual aspiration thrombectomy. Upfront intracoronary GP IIb/IIIa inhibitor (Tirofiban) was positively associated with improved myocardial reperfusion. Conclusion. Fully identifying risk factors will help to improve the effectiveness of selective thrombus aspiration.

Comparison of high glucose concentration blood and crystalloid cardioplegia in paediatric cardiac surgery: a randomized clinical trial.

OBJECTIVES: This study investigates the effects of high glucose content on patients undergoing cold crystalloid versus cold blood cardioplegia in terms of early clinical results, functional myocardial recovery and ischaemia-reperfusion injury in patients undergoing repair of acyanotic cardiac lesions. METHODS: Patients were randomly assigned to receive either crystalloid (n = 31) or blood cardioplegia (n = 31). Early clinical results were assessed. Changes in left ventricular fractional shortening, arterial blood lactate levels, central venous saturation, cardiac Troponin I release and blood glucose concentration were measured during the first 24 h after ischaemia. RESULTS: There was no significant difference in clinical outcomes and postoperative complication rates between groups. The postoperative changes in left ventricular function, lactate levels, central venous saturation and Troponin I were not significantly different between groups. The use of crystalloid cardioplegia was associated with significant increases in serum glucose compared with blood cardioplegia. CONCLUSIONS: A high glucose content blood cardioplegia does not show any advantage compared with crystalloid cardioplegia in terms of clinical outcomes, functional recovery and the degree of ischaemic injury in infants and children undergoing repair of acyanotic heart lesions. High glucose concentration of the cardioplegic solution might potentiate ischaemia-reperfusion injury and diminish the beneficial effects of blood cardioplegia.

Roles of Testosterone Replacement in Cardiac Ischemia-Reperfusion Injury.

Testosterone is an anabolic steroid hormone, which is the major circulating androgen hormone in males. Testosterone levels decreasing below the normal physiological levels lead to a status known as androgen deficiency. Androgen deficiency has been shown to be a major risk factor in the development of several disorders, including obesity, metabolic syndrome, and ischemic heart disease. In the past decades, although several studies from animal models as well as clinical studies demonstrated that testosterone exerted cardioprotection, particularly during ischemia-reperfusion (I/R) injury, other preclinical and clinical studies have shown an inverse relationship between testosterone levels and cardioprotective effects. As a result, the effects of testosterone replacement on the heart remain controversial. In this review, reports regarding the roles of testosterone replacement in the heart following I/R injury are comprehensively summarized and discussed. At present, it may be concluded that chronic testosterone replacement at a physiological dose demonstrated cardioprotective effects, whereas acute testosterone replacement can cause adverse effects in the I/R heart.

Predictors and impact of myocardial injury after transcatheter aortic valve replacement: a multicenter registry.

BACKGROUND: Cardiac biomarker release signifying myocardial injury post-transcatheter aortic valve replacement (TAVR) is common, yet its clinical impact within a large TAVR cohort receiving differing types of valve and procedural approaches is unknown. OBJECTIVES: This study sought to determine the incidence, clinical impact, and factors associated with cardiac biomarker elevation post TAVR. METHODS: This multicenter study included 1,131 consecutive patients undergoing TAVR with balloon-expandable (58%) or self-expandable (42%) valves. Transfemoral and transapical (TA) approaches were selected in 73.1% and 20.3% of patients, respectively. Creatine kinase-myocardial band (CK-MB) measurements were obtained at baseline and at several time points within the initial 72 h post TAVR. Echocardiography was performed at baseline and at 6- to 12-month follow-up. RESULTS: Overall, 66% of the TAVR population demonstrated some degree of myocardial injury as determined by a rise in CK-MB levels (peak value: 1.6-fold [interquartile range (IQR): 0.9 to 2.8-fold]). A TA approach and major procedural complications were independently associated with higher peak of CK-MB levels (p < 0.01 for all), which translated into impaired systolic left ventricular function at 6 to 12 months post TAVR (p < 0.01). A greater rise in CK-MB levels independently associated with an increased 30-day, late (median of 21 [IQR: 8 to 36] months) overall and cardiovascular mortality (p < 0.001 for all). Any increase in CK-MB levels was associated with poorer clinical outcomes, and there was a stepwise rise in late mortality according to the various degrees of CK-MB increase after TAVR (p < 0.001). CONCLUSIONS: Some degree of myocardial injury was detected in two-thirds of patients post TAVR, especially in those undergoing TA-TAVR or presenting with major procedural complications. A greater rise in CK-MB levels associated with greater acute and late mortality, imparting a negative impact on left ventricular function.

Antidiabetic treatment with gliptins: focus on cardiovascular effects and outcomes.

The traditional oral pharmacological therapy for type 2 diabetes mellitus (T2DM) has been based on the prescription of metformin, a biguanide, as first line antihyperglycemic agent world over. It has been demonstrated that after 3 years of treatment, approximately 50% of diabetic patients could achieve acceptable glucose levels with monotherapy; but by 9 years this had declined to only 25%. Therefore, the implementation of a combined pharmacological therapy acting via different pathways becomes necessary, and its combination with a compound of the sulfonylurea group was along decades the most frequently employed prescription in routine clinical practice. Meglitinides, glitazones and alpha-glucosidase inhibitors were subsequently developed, but the five mentioned groups of oral antihyperglycemic agents are associated with variable degrees of undesirable or even severe cardiovascular events. The gliptins-also called dipeptidyl peptidase 4 (DPP4) inhibitors--are an additional group of antidiabetic compounds with increasing clinical use. We review the status of the gliptins with emphasis on their capabilities to positively or negatively affect the cardiovascular system, and their potential involvement in major adverse cardiovascular events (MACE). Alogliptin, anagliptin, linagliptin, saxagliptin, sitagliptin, teneligliptin and vildagliptin are the compounds currently in clinical use. Regardless differences in chemical structure and metabolic pathways, gliptins as a group exert favorable changes in experimental models. These changes, as an almost general rule, include improved endothelial function, reduction of inflammatory markers, oxidative stress ischemia/reperfusion injury and atherogenesis. In addition, increased adiponectin levels and modest decreases in lipidemia and blood pressure were reported. In clinical settings, several trials--notably the longer one, employing sitagliptin, with a mean follow-up period of 3 years--did not show an increased risk for ischemic events. Anyway, it should be emphasized that the encouraging results from basic science were not yet translated into clinical evidence, probably due the multiple and pleiotropic enzymatic effects of DPP4 inhibition. Moreover, when employing saxagliptin, while the drug was not associated with an augmented risk for ischemic events, it should be pinpointed that the rate of hospitalization for heart failure was significantly increased. Gliptins as a group constitute a widely accepted therapy for the management of T2DM, usually as a second-line medication. Nonetheless, for the time being, a definite relationship between gliptins treatment and improved cardiovascular outcomes remains uncertain and needs yet to be proven.