Intravenous ferric carboxymaltose does not provide benefits in reperfused acute myocardial infarction in the rat with normal iron status.

BACKGROUND: Iron deficiency has been implicated in the pathophysiology of heart failure and myocardial ischemia and reperfusion injury. Moreover, reperfused heart seems to lose iron, thus even subjects with normal iron status could benefit from iron therapy. Impaired mitochondrial respiration and energy starvation may be among possible consequences of myocardial iron deficiency. So far no attempts have been made to treat acute coronary syndromes with iron. Thus our aim was to verify the hypothesis that intravenous iron therapy given during reperfusion of an acute myocardial infarction will reduce left ventricular remodeling and hemodynamic abnormalities in a 2-month follow-up as well as early mitochondrial dysfunction and mortality, in the rat with normal iron status. METHODS AND RESULTS: A single dose of ferric carboxymaltose was administered intravenously at 30 min of reperfusion following 30 min of ischemia in the rat model of myocardial infarction. Ventricular arrhythmias were monitored using a telemetric system, activity of mitochondrial enzymes was assessed using spectrophotometry, serum markers of oxidative stress and inflammation were determined and left ventricular function and remodeling were monitored using echocardiography and pressure-volume loops. Intravenous iron therapy did not affect post-myocardial infarction mortality, left ventricular size or function, ventricular arrhythmias, activity of mitochondrial respiratory chain, oxidative stress or markers of inflammation, but was not associated with any adverse effects. CONCLUSIONS: Although ferric carboxymaltose given at reperfusion was safe, it was ineffective in this model of reperfused myocardial infarction in the rat with normal iron status.

Autologous mitochondrial transplantation for cardiogenic shock in pediatric patients following ischemia-reperfusion injury.

OBJECTIVES: To report outcomes in a pilot study of autologous mitochondrial transplantation (MT) in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI). METHODS: A single-center retrospective study of patients requiring ECMO for postcardiotomy cardiogenic shock following IRI between May 2002 and December 2018 was performed. Postcardiotomy IRI was defined as coronary artery compromise followed by successful revascularization. Patients undergoing revascularization and subsequent MT were compared with those undergoing revascularization alone (Control). RESULTS: Twenty-four patients were included (MT, n = 10; Control, n = 14). Markers of systemic inflammatory response and organ function measured 1 day before and 7 days following revascularization did not differ between groups. Successful separation from ECMO-defined as freedom from ECMO reinstitution within 1 week after initial separation-was possible for 8 patients in the MT group (80%) and 4 in the Control group (29%) (P = .02). Median circumferential strain immediately following IRI but before therapy was not significantly different between groups. Immediately following separation from ECMO, ventricular strain was significantly better in the MT group (-23.0%; range, -20.0% to -28.8%) compared with the Control group (-16.8%; range, -13.0% to -18.4%) (P = .03). Median time to functional recovery after revascularization was significantly shorter in the MT group (2 days vs 9 days; P = .02). Cardiovascular events were lower in the MT group (20% vs 79%; P < .01). Cox regression analysis showed higher composite estimated risk of cardiovascular events in the Control group (hazard ratio, 4.6; 95% confidence interval, 1.0 to 20.9; P = .04) CONCLUSIONS: In this pilot study, MT was associated with successful separation from ECMO and enhanced ventricular strain in patients requiring postcardiotomy ECMO for severe refractory cardiogenic shock after IRI.

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.

Acute metformin treatment provides cardioprotection via improved mitochondrial function in cardiac ischemia / reperfusion injury.

Cardiac ischemia/reperfusion (I/R) injury following reperfusion therapy in acute myocardial infarction results in mitochondrial dynamic imbalance and cardiomyocyte apoptosis. Although diabetic patients taking metformin have been shown to have a lower risk of myocardial infarction, the efficacy of the cardioprotection conferred by metformin regarding the mitochondrial function and dynamic in cardiac I/R injury are still inconclusive. In addition, the comparative effects between different doses of metformin given acutely prior to cardiac I/R injury have never been investigated. Fifty 8-week-old male Wistar rats weighing 300-350 g were divided into sham-operated (n = 10) and cardiac I/R-operated (n = 40) groups. In the cardiac I/R group, rats underwent 30-min ischemia followed by 120-min reperfusion and were randomly divided into four subgroups (n = 10/group): control (received normal saline), metformin (100, 200, and 400 mg/kg). The arrhythmia score, cardiac function, infarct size, mortality rate, mitochondrial function and apoptosis, were determined. Metformin (200 mg/kg) exerted the highest level of cardioprotection through reduction in arrhythmia, infarct size, mitochondrial fission, and apoptosis, in addition to preservation of mitochondrial function, leading to the attenuation of cardiac dysfunction. Doses of metformin (100 and 400 mg/kg) also improved mitochondrial and cardiac function, but to a lesser extent than metformin (200 mg/kg). In conclusion, metformin exerts cardioprotection by attenuating mitochondrial dysfunction, mitochondrial dynamic imbalance, and apoptosis. These led to decreased infarct size and eventual improvement in cardiac function in rats with acute cardiac I/R injury. These findings indicate the potential clinical benefits of acute metformin treatment in acute myocardial infarction.

Anesthesia Protocols used to Create Ischemia Reperfusion Myocardial Infarcts in Swine.

The porcine ischemia-reperfusion model is one of the most commonly used for cardiology research and for testing interventions for myocardial regeneration. In creating ischemic reperfusion injury, the anesthetic protocol is important for assuring hemodynamic stability of the animal during the induction of the experimental lesion and may affect its postoperative survival. This paper reviews the many drugs and anesthetic protocols used in recent studies involving porcine models of ischemiareperfusion injury. The paper also summarizes the most important characteristics of some commonly used anesthetic drugs. Literature was selected for inclusion in this review if the authors described the anesthetic protocol used and also reported the mortality rate attributed to the creation of the model. This information is an important consideration because the anesthetic protocol can influence hemodynamic stability during the experimental induction of an acute myocardial infarction, thereby impacting the survival rate and affecting the number of animals needed for each study.

Neiguan (PC6)-based acupuncture pretreatment for myocardial ischemia reperfusion injury: A protocol for preclinical systematic review and meta-analysis.

BACKGROUND: Myocardial ischemia reperfusion injury (MIRI) is 1 of the leading causes of disability and mortality worldwide in the cardiovascular diseases. Acupuncture has been widely applied in the treatment and prevention of cardiovascular diseases in recent years. This systematic review protocol aims to provide the methods for evaluating the efficacy of Neiguan (PC6)-based acupuncture pretreatment in animal models of MIRI. METHODS AND ANALYSIS: The electronic databases of PubMed, Embase, Cochrane Library, as well as the Chinese databases such as China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, China Biology Medicine Database and WanFang Database will be searched from inception to November 2019. The outcome measures were myocardial infarct size, the level of ST-segment elevation, left ventricular ejection fraction, shortening fraction, arrhythmia score, cardiac enzymes, and cardiac troponin. Study inclusion, data extraction and quality assessment will be performed independently by 2 reviewers. RevMan 5.3 software will be used for the data synthesis and the quality of each study will be assessed independently by using the Collaborative Approach To Meta-Analysis And Review Of Animal Data From Experimental Studies checklist with minor modification. RESULTS: This review will provide a high-quality synthesis of Neiguan (PC6)-based acupuncture pretreatment for MIRI in animal models CONCLUSIONS:: This systematic review will provide conclusive evidence for whether Neiguan (PC6)-based acupuncture pretreatment is an effective intervention in animal models of MIRI. TRIAL REGISTRATION NUMBER: PROSPERO CRD42020175144.

Effect of remote ischemic preconditioning in patients with STEMI during primary percutaneous coronary intervention: a meta-analysis of randomized controlled trials.

Remote ischemic conditioning is usually associated with cardioprotective intervention against ischemia-reperfusion. However, the effect of remote ischemic preconditioning (RIC-pre) completed before myocardial reperfusion with intermittent limb ischemia-reperfusion in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) is unclear. PubMed, EMBASE, and the Cochrane Library were fully searched from the beginning of each database up to September 2019 to find seven RCTs, a total of 2796 patients with STEMI undergoing PPCI with RIC-pre and 2818 patients with STEMI undergoing PPCI alone. No significant discrepancy in cardiac death was observed between RIC-pre and control groups (RR 1.03, 95% CI [0.76-1.41], P = 0.83, I2 = 40%). The incidences of hospitalization for heart failure (RR 1.03, 95% CI [0.85-1.25], P = 0.77, I2 = 0%), myocardial infarction (RR 0.86, 95% CI [0.59-1.26], P = 0.44, I2 = 0%), and stroke (RR 1.04, 95% CI [0.62-1.77], P = 0.87, I2 = 0%) were not decreased in RIC-pre group when compared with control group. Subgroup analysis revealed similar risk in clinical adverse events at long- and short-term follow-up between two groups. However, peak of creatine kinase-myocardial band (CK-MB) was reduced in RIC-pre group (SWD -0.42, 95% CI [-0.77, -0.07], P = 0.02, I2 = 34%). RIC-pre tended to a low peak of CK-MB in patients with STEMI undergoing PPCI, but lacked significant beneficial effects on improving clinical outcomes at long- and short-term follow-up.

Intracoronary compared with intravenous bolus tirofiban on the microvascular obstruction in patients with STEMI undergoing PCI: a cardiac MR study.

To investigate the potential effect of intracoronary administration of the glycoprotein IIb/IIIa inhibitor tirofiban on the microvascular obstruction (MVO) assessed by cardiac magnetic resonance (CMR) imaging compared to the intravenous route in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). Two hundred eight patients were randomized into two groups (tirofiban i.v. and tirofiban i.c.). CMR was completed within 3-7 days after ST-segment-elevation myocardial infarction. One hundred thirty-two patients had a follow-up CMR at 6 months after discharge. The primary end point was the CMR measurements including myocardium strain, myocardial perfusion index, final infarct size, prevalence and extent of MVO, and the change of left ventricular end-diastolic volume (LVEDV) at six months follow-up. The second endpoint was major adverse cardiovascular events (composite of all-cause death, nonfatal reinfarction and congestive heart failure) in one year. The MVO prevalence and extent [56% versus 36%, p = 0.004; 2.08 (IQR: 1.18-5.07) g versus 1.68 (IQR: 0.30-3.28) g, p = 0.041] showed a significant difference between the intravenous and intracoronary groups. Global left ventricular peak longitudinal strain was significantly different in intracoronary groups compared to intravenous groups, - 12.5 [IQR: - 13.4 to - 10.9] versus - 12.3 [IQR: - 13.4 to - 10.4], respectively (P = 0.042). Infarcted myocardial perfusion index was significantly different in intracoronary groups compared to intravenous groups, 0.11 [IQR: 0.08 to 0.15] versus 0.09 [IQR: 0.07 to 0.14], respectively (P = 0.026). Intracoronary tirofiban was associated with a higher change in LVEDV compared with intravenous group (- 10.2% [IQR: - 13.7% to - 2.6%] versus 1.3% [IQR: - 5.6% to 6.1%], p < 0.001). Intracoronary tirofiban application showed no benefit on the occurrence of major adverse cardiovascular events during follow-up compared to intravenous administration. This CMR study in ST-segment-elevation myocardial infarction patients showed a benefit in MVO and left ventricular remodeling for intracoronary tirofiban administration compared to intravenous administration in patients undergoing PCI.

Remote Ischemic Conditioning in Acute Myocardial Infarction and Shock States.

Remote ischemic conditioning is the phenomenon whereby brief, nonlethal episodes of ischemia in one organ (such as a limb) protect a remote organ from ischemic necrosis induced by a longer duration of severe ischemia followed by reperfusion. This phenomenon has been reproduced by dozens of experimental laboratories and was shown to reduce the size of myocardial infarction in many but not all clinical studies. In one recent large clinical trial, remote ischemic conditioning induced by repetitive blood pressure cuff inflations on the arm did not reduce infarct size or improve clinical outcomes. This negative result may have been related in part to the overall success of early reperfusion and current adjunctive therapies, such as antiplatelet therapy, antiremodeling therapies, and low-risk patients, that may make it difficult to show any advantage of newer adjunctive therapies on top of existing therapies. One relevant area in which current outcomes are not as positive as in the treatment of heart attack is the treatment of shock, where mortality rates remain high. Recent experimental studies show that remote ischemic conditioning may improve survival and organ function in shock states, especially hemorrhagic shock and septic shock. In this study, we review the preclinical studies that have explored the potential benefit of this therapy for shock states and describe an ongoing clinical study.

The Relationship between the Use of Cold and Isothermic Blood Cardioplegia Solution for Myocardial Protection during Cardiopulmonary Bypass and the Ischemia-Reperfusion Injury.

PURPOSE: In this study, we aimed to assess myocardial protection and ischemia-reperfusion injury in patients undergoing open heart surgery with isothermic blood cardioplegia (IBC) or hypothermic blood cardioplegia (HBC). MATERIALS AND METHODS: A total of 48 patients who underwent isolated coronary artery bypass grafting or isolated mitral valve surgery between March 2017 and October 2017 were evaluated as randomized prospective study. Study groups (HBC: Group 1, IBC: Group 2) were compared in terms of interleukin 6 (IL-6), IL-8, IL-10, and complement factor 3a (C3a) levels, metabolic parameters, creatine kinase-muscle/brain (CK-MB) and high-sensitivity Troponin I (hsTn-I), and clinical outcomes. RESULTS: Comparison of the markers of ischemia-reperfusion injury showed significantly higher levels of the proinflammatory cytokine IL-6 in the early postoperative period as well as IL-8, in Group 2 (p <0.001), whereas the anti-inflammatory cytokine IL-10 was significantly higher during the X1 time period (p = 0.11) in Group 2, and subsequently it was higher in Group 1. Using myocardial temperature probes, the target myocardial temperatures were measured in the patients undergoing open heart surgery with different routes of cardioplegia, and significant differences were noted (p = 0.000). CONCLUSION: HBC for open heart surgery is associated with less myocardial injury and intraoperative and postoperative morbidity, indicating superior myocardial protection versus IBC.

Do We Need Potent Intravenous Antiplatelet Inhibition at the Time of Reperfusion During ST-Segment Elevation Myocardial Infarction?

Acute myocardial infarction (MI) is still a large source of morbidity and mortality worldwide. Although early reperfusion therapy has been prioritized in the modern era of percutaneous coronary intervention and thrombolysis, attempts at incremental improvements in clinical outcomes by reducing MI size have not been successful so far. Herein, we review the studies that have evaluated immediate-onset antiplatelet therapy as attempts to improve meaningful clinical outcomes in ST-segment elevation MI (STEMI). Unfortunately, many of the adjunctive pharmacotherapies have proven to be disappointing. Recent studies performed in the background of routine oral administration of P2Y12 adenosine receptor inhibitors, which may take several hours to take full effect, and aspirin have largely shown no improvement in outcomes, despite an earlier onset of antiplatelet activity of the investigative agents. Further progress in improving outcomes during STEMI may depend on exploring therapeutics that modulate the pathophysiology of microvascular damage during ischemia-reperfusion injury, a phenomenon whose effects evolve over hours to days. We speculate that the dynamic nature of the no-reflow phenomenon may be an explanation for these disappointing results with the intravenous antiplatelet agents. We hope that appreciation for what has not worked in this domain may direct future research efforts to focus on novel pathways. Myocardial ischemia and reperfusion injury are very much still a lingering issue. Despite significant improvements in door-to-balloon times, rates of in-hospital mortality for STEMI remain unchanged. Outcomes following successfully reperfused STEMI are likely determined by the initial size of myocardial necrosis (ie, cardiomyocyte death during the period of ongoing ischemia), patency of the infarct-related epicardial coronary artery, possible reperfusion injury, the microvascular no-reflow phenomenon, and adverse remodeling after infarction.

Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights.

OBJECTIVES: The aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI). BACKGROUND: The pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood. METHODS: Patients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used. RESULTS: In total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post-percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99). CONCLUSIONS: Smoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850).

Exercise and Cardioprotection: A Natural Defense Against Lethal Myocardial Ischemia-Reperfusion Injury and Potential Guide to Cardiovascular Prophylaxis.

Similar to ischemic preconditioning, high-intensity exercise has been shown to decrease infarct size following myocardial infarction. In this article, we review the literature on beneficial effects of exercise, exercise requirements for cardioprotection, common methods utilized in laboratories to study this phenomenon, and discuss possible mechanisms for exercise-mediated cardioprotection.

Low-Volume Cardioplegia and Myocardial Protection in Coronary Artery Bypass Graft Surgery.

We studied myocardial protection during coronary artery bypass graft surgery using low-volume cardioplegia (Cardioplexol) and minimal extracorporeal circulation (MECC) for different types of coronary artery diseases. In total, 426 consecutive patients were included and divided into four groups: those with left main stem stenosis (n = 45), those with three-vessel disease (n = 200), those with both (n = 141), and those with neither (n = 40). The peak postoperative myocardial markers and 30-day mortality were analyzed. Both myocardial markers and 30-day mortality were significantly elevated in patients with isolated main stem stenosis. We conclude that the use of low-volume cardioplegia and MECC is safe. However, patients with underlying isolated left main stem stenosis might be less protected.

Relation of Chronic Myocardial Injury and Non-ST-Segment Elevation Myocardial Infarction to Mortality.

The prognosis in patients with chest pain and chronic myocardial injury compared with patients with non-ST-segment elevation myocardial infarction (NSTEMI) is unknown. This study aims to investigate differences in long-term outcomes. Patients with chest pain at Karolinska University Hospital, Sweden from 2011 to 2014, who had stable high-sensitivity cardiac troponin T (hs-cTnT) levels were compared with patients with NSTEMI. We estimated hazard ratios with 95% confidence intervals for the risk of all-cause mortality, myocardial infarction, and heart failure at different hs-cTnT levels using patients with NSTEMI as referent. A total of 20,387 patients were included, of whom 927 had NSTEMI. Among 19,460 patients with stable hs-cTnT levels, 1,528 had chronic myocardial injury defined as stable hs-cTnT levels > 14 ng/L. Mean follow-up was 3.2 years. Patients with hs-cTnT levels of <5 and 5 to 9 ng/L had a lower risk, while patients with chronic myocardial injury with hs-cTnT levels of 30 to 49 and ≥50 ng/L had a higher risk of death (adjusted hazard ratios, 95% confidence intervals: 1.65, 1.30 to 2.10 and 2.13, 1.60 to 2.84, respectively) compared with patients with NSTEMI. Patients with hs-cTnT levels <15 ng/L had a lower risk of heart failure, with no difference in risk at higher hs-cTnT levels. All stable hs-cTnT levels were associated with a lower risk of myocardial infarction (MI). In conclusion, patients with chest pain and stable hs-cTnT levels 10 to 29 ng/L have a similar risk, and those with chronic myocardial injury with hs-cTnT levels of ≥30 ng/L have an increased risk of long-term all-cause mortality compared with patients with NSTEMI.

Cardioprotective Activity of 2,6-Diisobornyl-4-Methylphenol in Acute Myocardial Ischemia/Reperfusion in Rats.

We studied the cardioprotective effect of 2,6-diisobornyl-4-methylphenol under conditions of myocardial ischemia/reperfusion in rats. Daily administration of 2,6-diisobornyl-4-methylphenol (100 mg/kg intragastrically) over 3 days before and 5 days after modeling of myocardial ischemia/reperfusion prevented the increase in the infarction area by almost 2 times in comparison with the control by day 5 after recirculation. The type and severity of pathological changes in ECG parameters reflecting necrotic changes in the myocardium under the action of the compound significantly decreased by day 35 of the experiment. Animal survival rate during the first 24 h after ischemia/reperfusion modeling in the experimental group was by 29% higher than in the control group.

Markers of Reperfusion and Long-Term (8-Year) Prognosis after Primary Percutaneous Coronary Intervention.

Thrombolysis in Myocardial Infarction (TIMI) flow, myocardial perfusion grade (MPG), and infarct size are established markers of reperfusion in patients with ST-segment elevation myocardial infarction. Whether these markers provide long-term prognostic information remains unknown. This study included 1,406 patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention. Postreperfusion TIMI flow, MPG, and infarct size (evaluated by scintigraphy at 7 to 14 days) were measured. The primary outcome was 8-year mortality. Overall there were 190 deaths. The Kaplan-Meier estimates of mortality were 22.6% (37 deaths) and 16.8% (153 deaths) according to TIMI flow ≤2 and TIMI flow 3 (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.66 to 1.00, p = 0.058 for 1 grade increment), 21.6% (106 deaths) and 14.5% (84 deaths) according to MPG ≤2 and MPG 3 (adjusted HR 0.87 [0.77 to 0.98], p = 0.020 for 1 grade increment) and 21.7% (115 deaths) and 13.7% (75 deaths) according to infarct size >10% (median value) and infarct size ≤10% of the left ventricle (adjusted HR 1.08 [1.03 to 1.13], p = 0.001, for 5% of left ventricle increment in infarct size). The C statistic of the model for all-cause mortality was 0.810 (0.781 to 0.839) with baseline variables, 0.812 (0.783 to 0.841) after incorporation of TIMI flow (P for significance compared to the model with baseline variables = 0.140), 0.813 (0.784 to 0.841) after incorporation of MPG (p = 0.345) and 0.815 (0.786 to 0.842) after incorporation of infarct size (p = 0.08). In conclusion, markers of reperfusion independently predict long-term mortality after primary percutaneous coronary intervention but offer limited incremental prognostic value to that provided by evaluation of baseline cardiovascular risk factors and clinical data.

Remote Ischemic Preconditioning in High-risk Cardiovascular Surgery Patients: A Randomized-controlled Trial.

Remote ischemic preconditioning (RIPC) may reduce biomarkers of ischemic injury after cardiovascular surgery. However, it is unclear whether RIPC has a positive impact on clinical outcomes. We performed a blinded, randomized controlled trial to determine if RIPC resulted in fewer adverse clinical outcomes after cardiac or vascular surgery. The intervention consisted of 3 cycles of RIPC on the upper limb for 5 minutes alternated with 5 minutes of rest. A sham intervention was performed on the control group. Patients were recruited who were undergoing (1) high-risk cardiac or vascular surgery or (2) cardiac or vascular surgery and were at high risk of ischemic complications. The primary end point was a composite outcome of mortality, myocardial infarction, stroke, renal failure, respiratory failure, and low cardiac output syndrome, and the secondary end points included the individual outcome parameters that made up this score, as well as troponin-I values. A total of 436 patients were randomized and analysis was performed on 215 patients in the control group and on 213 patients in the RIPC group. There were no differences in the composite outcome between the 2 groups (RIPC: 67 [32%] and control: 72 [34%], relative risk [0.94 {0.72-1.24}]) or in any of the individual components that made up the composite outcome. Additionally, we did not observe any differences between the groups in troponin-I values, the length of intensive care unit stay, or the total hospital stay. RIPC did not have a beneficial effect on clinical outcomes in patients who had cardiovascular surgery.

Circadian dependence of manual thrombus aspiration benefit in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: The clinical benefit of manual thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) remains uncertain. This study assessed the impact of circadian rhythms on the effectiveness of manual TA. METHODS AND RESULTS: We conducted an observational study of patients enrolled in the Acute Myocardial Infarction in Switzerland Plus registry. STEMI patients undergoing PPCI with (TA group) or without (PCI-alone group) manual TA were divided based on time-of-day symptom onset: group 1 (00:00-05:59), group 2 (06:00-11:59), group 3 (12:00-17:59) and group 4 (18:00-23:59). The primary endpoint was circadian variation of myocardial infarction (MI) size. The secondary endpoint was in-hospital all-cause mortality. Between 2009 and 2014, 3648 patients underwent PPCI (TA, 49%). After propensity-score matching, 2860 patients were included. Minimal myocardial Injury was observed in groups 2 and 3 (peak creatine kinase level group 1, 2723 ± 148 U/l; group 2, 2493 ± 105 U/l; group 3, 2550 ± 106 U/l; group 4, 2952 ± 144 U/l; p = 0.044) in the TA group, whereas no time-of-day dependence was found in PCI-alone group. After periodic sinusoidal regression analysis, a circadian relationship between time-of-day symptom onset and MI size was demonstrated in the TA group (p < 0.001). In-hospital all-cause mortality was 3.4% in the TA group and 4.3% in the PCI-alone group (p = 0.20). CONCLUSIONS: In this large registry of STEMI patients, manual TA did not reduce in-hospital all-cause mortality. Nonetheless, there was a circadian dependence of TA effectiveness with greatest myocardial salvage for patients with symptom onset between 06:00 and 17:59.

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.