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BACKGROUND: Stroke is the second cause of mortality and the foremost leading cause of disability globally. Many potential biomarkers have been described to contribute to prognosticating the severity in the acute phase of stroke as well as help with risk stratification. Copeptin, an inactive peptide that is produced in an equimolar ratio to arginine vasopressin and adequately mirrors an individual's stress response to acute illnesses like acute ischaemic stroke as evidenced by elevated or increasing levels is being explored in this study to determine its relationship with acute stroke severity and infarct size on admission. METHODS: This is a cross-sectional study of 80 neuroimaging-confirmed acute ischaemic patients who presented within seven days of symptom onset and 80 control subjects. The ischaemic stroke cases had stroke severity and infarct volume determined on admission by the National Institute of Health Stroke Scale (NIHSS) and neuroimaging (brain CT/MRI). A baseline serum copeptin level was measured in the study subjects. Spearman correlation and Kruskal Wallis test were used to determine the relationship between serum copeptin level with admission NIHSS and infarct size respectively. The receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of copeptin to predict severity and outcome. RESULTS: The mean age of the study group was 61.3 ± 12.7 years with 55.0% males and 45.0% females. The serum level of copeptin was significantly higher in the stroke cases with a median of 28.6 pmol/L (interquartile range (IQR)- 15.4-31.6 pmol/L) versus 8.8 pmol/L (IQR- 3.2- 10.7 pmol/L) among the stroke-free controls (p= 0.001) at a statistically significant level. There was a weak correlation between copeptin and NIHSS calculated at admission to measure stroke severity (r- 0.02, p= 0.873). Patients with infarct sizes in the fourth quartile (infarct sizes greater than 18.78 cm3) had higher copeptin levels, though this was not statistically significant (H= 2.88; p= 0.410). Admission serum copeptin did not show a statistically significant prognostic value in predicting stroke severity and mortality in stroke patients who presented within seven days of symptom onset with an area under curve (AUC) of 0.51 (95% CI: 0.36-0.65; p= 0.982). CONCLUSION: In this study, copeptin was higher among the stroke cases compared with the stroke-free controls which suggests a significant prognostic value in risk stratification in the acute phase of stroke; however, this did not significantly correlate with stroke severity and thus warrants further study in this field to elucidate it's fascinating potential as a prognostic biomarker (especially in the acute period) as this may enable allocation of a better-focused therapy for stroke patients.
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The concept of left ventricular unloading has its foundation in heart physiology. In fact, the left ventricular mechanics and energetics represent the cornerstone of this approach. The novel sophisticated therapies for acute heart failure, particularly mechanical circulatory supports, strongly impact on the mechanical functioning and energy consuption of the heart, ultimately affecting left ventricle loading. Notably, extracorporeal circulatory life support which is implemented for life-threatening conditions, may even overload the left heart, requiring additional unloading strategies. As a consequence, the understanding of ventricular overload, and the associated potential unloading strategies, founds its utility in several aspects of day-by-day clinical practice. Emerging clinical and pre-clinical research on left ventricular unloading and its benefits in heart failure and recovery has been conducted, providing meaningful insights for therapeutical interventions. Here, we review the current knowledge on left ventricular unloading, from physiology and molecular biology to its application in heart failure and recovery.
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BACKGROUND: Sonothrombolysis is a therapeutic application of ultrasound with ultrasound contrast for patients with ST elevation myocardial infarction (STEMI). Recent trials demonstrated that sonothrombolysis, delivered before and after primary percutaneous coronary intervention (pPCI), increases infarct vessel patency, improves microvascular flow, reduces infarct size, and improves ejection fraction. However, it is unclear whether pre-pPCI sonothrombolysis is essential for therapeutic benefit. We designed a parallel 3-arm sham-controlled randomized controlled trial to address this. METHODS: Patients presenting with first STEMI undergoing pPCI within 6 hours of symptom onset were randomized 1:1:1 into 3 arms: sonothrombolysis pre-/post-pPCI (group 1), sham pre- sonothrombolysis post-pPCI (group 2), and sham pre-/post-pPCI (group 3). Our primary end point was infarct size (percentage of left ventricular mass) assessed by cardiac magnetic resonance imaging at day 4 ± 2. Secondary end points included myocardial salvage index (MSI) and echocardiographic parameters at day 4 ± 2 and 6 months. RESULTS: Our trial was ceased early due to the COVID pandemic. From 122 patients screened between September 2020 and June 2021, 51 patients (age 60, male 82%) were included postrandomization. Median sonothrombolysis took 5 minutes pre-pPCI and 15 minutes post-, without significant door-to-balloon delay. There was a trend toward reduction in median infarct size between group 1 (8% [interquartile range, 4,11]), group 2 (11% [7, 19]), or group 3 (15% [9, 22]). Similarly there was a trend toward improved MSI in group 1 (79% [64, 85]) compared to groups 2 (51% [45, 70]) and 3 (48% [37, 73]) No major adverse cardiac events occurred during hospitalization. CONCLUSIONS: Pre-pPCI sonothrombolysis may be key to improving MSI in STEMI. Multicenter trials and health economic analyses are required before clinical translation.
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AIMS: The Selvester scoring system has been derived from ECG parameters for estimating infarct size. However, there is still a lack of evidence for Selvester score as an alternative to cardiac magnetic resonance (CMR) myocardial injury makers for risk stratification and prediction of left ventricular function (LVF) recovery among patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: This multicentre observational study enrolled 328 STEMI patients (88.4% men, 57.3 ± 10.6 years of age) undergoing CMR examination 1 week post-reperfusion therapy. Patients with baseline left ventricular ejection fraction (LVEF) < 50% underwent a follow-up CMR 6 months later, categorized into baseline normal LVF (ejection fraction [EF] ≥ 50% at baseline, n = 155); recovered LVF (EF < 50% at baseline and ≥50% after 6 months, n = 69); and reduced LVF (EF < 50% at baseline and after 6 months, n = 104). The median follow-up was 4 (3-4) years for all patients, with 61 patients experiencing major adverse cardiovascular event (MACEs). Patients with reduced LVF had a higher risk of MACEs than those with baseline normal LVF (P = 0.01), while the recovered LVF group had no significant difference (P > 0.05). A Selvester score >10 doubled the risk of MACEs in patients with systolic dysfunction (1.91 [1.02 to 3.58], P = 0.04). Additionally, Selvester score, baseline LVEF, transmural infarction, and peak CK-MB were independent predictors of recovered LVF, with Selvester score providing incremental predictive value to peak CK-MB in predicting recovered LVF (∆AUC = 0.07, P < 0.05). CONCLUSIONS: The Selvester score improves risk stratification among STEMI patients beyond LVEF and provide independent and incremental information to clinical parameters in predicting recovered LVF.
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Background: Coronary microvascular dysfunction is associated with adverse prognosis after ST-segment elevation myocardial infarction (STEMI). We aimed to compare the invasive, Doppler wire-based coronary flow reserve (CFR) with the non-invasive transthoracic Doppler echocardiography (TTDE)-derived CFR, and their ability to predict infarct size. Methods: We included 36 patients with invasive Doppler wire assessment on days 3-7 after STEMI treated with primary percutaneous coronary intervention (PCI), of which TTDE-derived CFR was measured in 47 vessels (29 patients) within 6 h of the invasive Doppler. Infarct size was assessed by cardiac magnetic resonance at a median of 8 months. Results: The correlation between invasive and non-invasive CFR was modest in the overall cohort (rho 0.400, p = 0.005). It improved when only measurements in the LAD artery were considered (rho 0.554, p = 0.002), with no significant correlation in the RCA artery (rho -0.190, p = 0.435). Both invasive (AUC 0.888) and non-invasive (AUC 0.868) CFR, measured in the recanalized culprit artery, showed a good ability to predict infarct sizes ≥18% of the left ventricular mass, with the optimal cut off values of 1.85 and 1.80, respectively. Conclusions: In patients with STEMI, TTDE- and Doppler wire-derived CFR exhibit significant correlation, when measured in the LAD artery, and both have a similarly strong association with the final infarct size.
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Background: The effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on ischemia reperfusion injury (IRI) is a novel concept and only limited number of animals studies have yet been investigated. We aimed to perform a systematic review of literature to explore the clinical studies which investigated the effects of SGLT-2 inhibitors on myocardial IRI setting.Methods: We searched MEDLINE, Embase, and Cochrane Library from inception until December 7th, 2023. ClinicalTrials.gov was also explored for ongoing studies. Two authors independently conducted the literature search, examined the studies, and evaluated the eligibility criteria. Any disagreements or uncertainties were resolved by the corresponding author. The search strategy followed the PICO process (Population, Intervention, Comparison, and Outcome) and Emtree was used to select relevant keywords.Results: Of 220 articles identified from the literature research, five articles were included in the study, of which three studies lately were retracted. The remaining studies included 1229 participants, with 209 receiving SGLT-2 inhibitors and 1090 not receiving them. All of the participants were diabetic patients admitted with acute myocardial infarction (AMI), undergoing percutaneous coronary intervention (PCI). The results demonstrated that the use of SGLT-2 inhibitors is associated with lower troponin levels, and higher rates of ST resolution. The results of the studies also showed smaller infarct sizes, lower inflammatory biomarkers and improved left ventricular function at discharge among SGLT-2 inhibitor users.Conclusion: In line with in vivo and ex vivo findings, the results of this systematic review supported benefits of SGLT-2 inhibitors in IRI through reducing infarct size and inflammatory biomarkers. However, further clinical trials are warranted to provide robust evidence.
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BACKGROUND: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention. METHODS: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore. Patients were randomized to receive either cangrelor or placebo initiated before the primary percutaneous coronary intervention procedure on top of oral ticagrelor. The key exclusion criteria included presenting <6 hours of symptom onset; previous MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance. The primary efficacy end point was acute MI size by cardiovascular magnetic resonance within the first week expressed as percentage of the left ventricle mass (%LVmass). Microvascular obstruction was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety end point was Bleeding Academic Research Consortium-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test (reported as median [first quartile-third quartile]), and categorical variables were compared by Fisher exact test. A 2-sided P<0.05 was considered statistically significant. RESULTS: Of 209 recruited patients, 164 patients (78%) completed the acute cardiovascular magnetic resonance scan. There were no significant differences in acute MI size (placebo, 14.9% [7.3-22.6] %LVmass versus cangrelor, 16.3 [9.9-24.4] %LVmass; P=0.40) or the incidence (placebo, 48% versus cangrelor, 47%; P=0.99) and extent of microvascular obstruction (placebo, 1.63 [0.60-4.65] %LVmass versus cangrelor, 1.18 [0.53-3.37] %LVmass; P=0.46) between placebo and cangrelor despite a 2-fold decrease in platelet reactivity with cangrelor. There were no Bleeding Academic Research Consortium-defined major bleeding events in either group in the first 48 hours. CONCLUSIONS: Cangrelor administered at the time of primary percutaneous coronary intervention did not reduce acute MI size or prevent microvascular obstruction in patients with ST-segment-elevation MI given oral ticagrelor despite a significant reduction of platelet reactivity during the percutaneous coronary intervention procedure. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03102723.
Subject(s)
Adenosine Monophosphate , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Male , Female , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/drug therapy , ST Elevation Myocardial Infarction/diagnostic imaging , Middle Aged , Double-Blind Method , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adenosine Monophosphate/administration & dosage , Aged , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Treatment Outcome , Singapore , Ticagrelor/therapeutic use , Ticagrelor/administration & dosageABSTRACT
The present analysis reports on the robustness of preclinical cardioprotection studies with infarct size as endpoint which were published in Basic Research in Cardiology, Cardiovascular Research, and Circulation Research between January 2013 and December 2023. Only 26 out of 269 papers with technically robust analysis of infarct size by triphenyltetrazolium chloride staining, magnetic resonance imaging or single photon emission tomography applied a prospective power analysis. A retrospective power calculation revealed that only 75% of the reported data sets with statistically significant positive results from all these studies had a statistical power of ≥ 0.9, and an additional 9% had a statistical power ≥ 0.8. The remaining 16% of all significant positive data sets did not even reach the 0.8 threshold. Only 13% of all analyzed data sets were neutral. We conclude that neutral studies are underreported and there is indeed a significant lack of robustness in many of the published preclinical cardioprotection studies which may contribute to the difficulties of translating cardioprotection to patient benefit.
Subject(s)
Publication Bias , Animals , Humans , Myocardial Infarction/prevention & control , Myocardial Infarction/pathology , Myocardial Infarction/diagnostic imaging , Disease Models, Animal , Cardiotonic Agents/therapeutic useABSTRACT
INTRODUCTION: It is still uncertain if higher thresholds on National Institute of Health Stroke Scale (NIHSS) are better predictors of large infarctions than the conventional 6-point cutoff. METHODS: We used 6-point and higher NIHSS thresholds including 8, 9, and 10-point to predict relative infarct areas, expressed as percentage of the affected hemisphere on axial brain computed tomography images, beginning at 5% with 5% increments each time until reaching the 40% cutoff for large infarctions, or achieving 100% sensitivity. Results were compared using area under the receiver operating characteristic curves (AUROC). RESULTS: We enrolled 151 patients of acute ischemic stroke (Mean age: 62.88 years ± 12.71; Female: 48.34%). 77 patients (50.99%) exhibited left hemisphere strokes, while 74 (49%) had right hemisphere involvement. Sensitivity values of the 6-point for infarcts measuring 5%, 10%, 20%, 30%, and 40% were 62%, 64%, 77%, 82%, and 100%, respectively. At 40% infarct-size, 8-point achieved comparable results (52%, 55%, 69%, 76%, 100%), closely aligning with the 9-point (50%, 53%, 69%, 76%, 100%). The10-point was slightly trailing behind in sensitivity at 40% infarct-core (96%). Moreover, higher thresholds exhibited improved false-positive rates (FPR). At 40% infarct size, the FPRs of 6, 8, 9, and 10 points were 39%, 27%, 27%, and 21% respectively. Higher thresholds had augmented AUROC values (0.86, 0.86, 0.89) as compared to the 6-point (0.80). Logistic regression identified 14-point as definitive cutoff for large infarctions. CONCLUSION: Higher thresholds can better differentiate small and medium infarcts as true-negatives and substantially reduce false-positive referrals for mechanical thrombectomy.
Subject(s)
Ischemic Stroke , Humans , Female , Male , Middle Aged , Aged , Reproducibility of Results , Ischemic Stroke/diagnostic imaging , Severity of Illness Index , Stroke/diagnostic imaging , Tomography, X-Ray Computed , National Institutes of Health (U.S.) , Sensitivity and Specificity , Aged, 80 and overABSTRACT
Ischemic heart disease (IHD) is the leading cause of mortality worldwide and can be complicated by myocardial infarction (MI), leading to cardiac failure. Inorganic nitrite and nitrate, which release nitric oxide (NO), can protect the heart against myocardial injury. This animal systematic review and meta-analysis aims to assess whether the administration of nitrite/nitrate decreases myocardial infarct size. We systematically searched PubMed, Scopus, and Web of Science databases until October 2023; 15 eligible animal studies (35 study arms for in-vivo and 10 for in-vitro studies) published between 1989 and 2023 were included. In-vivo studies were conducted on rats, mice, cats, and dogs, and in-vitro studies on rats and mice with an overall exposure of 0.03 to 12713 mg/kg to nitrate/nitrite administrated before, after, or during ischemia mainly by intravenous single bolus or by oral over 270 days. All in-vitro studies used nitrite/nitrate before ischemia, with the concentration ranging between 0.34 to 201 µM. MI was induced by occlusion of the left anterior diagonal or left circumflex arteries in in-vitro studies and by isoproterenol in in-vivo studies. Infarct size was measured by direct staining of the sliced heart sections. In in-vivo studies, nitrite (overall effect size (ES)=-17.0 %, 95 % confidence interval (CI)=-21.3, -12.8, P<0.001) and nitrate (overall ES= -9.6 %, 95 % CI=-15.7, -3.4, P=0.002) reduced myocardial infarct size. In in-vitro studies, nitrite (overall ES=-15.8 %, 95 % CI=-25.5, -6.2, P=0.001) reduced the infarct size. Sensitivity analysis showed that the overall effect of nitrite on myocardial infarct size was unaffected by doses or health conditions in in-vivo and in-vitro studies. In conclusion, our meta-analysis showed that nitrite/nitrate administration can effectively reduce myocardial infarct size. However, these results should be approached with caution because of the limitations of animal studies and the existing high heterogeneity.
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We aimed to assess the correlation of cardiovascular magnetic resonance (CMR)-derived epicardial adipose tissue (EAT) with infarct size (IS) and residual systolic function in ST-segment elevation myocardial infarction (STEMI). We enrolled patients discharged for a first anterior reperfused STEMI submitted to undergo CMR. EAT, left ventricular (LV) ejection fraction (LVEF), and IS were quantified at the 1-week (n = 221) and at 6-month CMR (n = 167). At 1-week CMR, mean EAT was 31 ± 13 mL/m2. Patients with high EAT volume (n = 72) showed larger 1-week IS. After adjustment, EAT extent was independently related to 1-week IS. In patients with large IS at 1 week (>30% of LV mass, n = 88), those with high EAT showed more preserved 6-month LVEF. This association persisted after adjustment and in a 1:1 propensity score-matched patient subset. Overall, EAT decreased at 6 months. In patients with large IS, a greater reduction of EAT was associated with more preserved 6-month LVEF. In STEMI, a higher presence of EAT was associated with a larger IS. Nevertheless, in patients with large infarctions, high EAT and greater subsequent EAT reduction were linked to more preserved LVEF in the chronic phase. This dual and paradoxical effect of EAT fuels the need for further research in this field.
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This comprehensive case report documents the treatment of a 37-year-old female patient who presented with anterior ST-elevation myocardial infarction (STEMI). The patient underwent percutaneous coronary intervention (PCI), followed by an innovative therapy - optimized supersaturated oxygen therapy (SSO2). This therapy was chosen due to its potential to enhance myocardial salvage, particularly in severe MI cases like the patient. The report meticulously details the patient's clinical course, including the diagnostic procedures and the rationale behind opting for SSO2 therapy. It highlights the significant improvements observed post-therapy: enhanced left ventricular (LV) function and a remarkable reduction in the size of the LV apical aneurysm. These outcomes suggest a direct benefit of SSO2 in reducing myocardial damage. Finally, the report discusses the broader implications of these findings. It underscores the potential of optimized SSO2 therapy in clinical settings, particularly for patients with anterior MI. The case exemplifies how advanced therapeutic interventions like SSO2 can play a pivotal role in improving clinical outcomes post-MI, thereby advocating for its consideration in similar clinical scenarios.
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OBJECTIVE: Myocardial infarction (MI) is one of the leading causes of death in the world. Early myocardial reperfusion improves acute MI survival. Bioflavonoid quercetin is known to have antioxidant, anti-inflammatory, and anti-proliferative properties. The presented pilot study aims to investigate the cardioprotective effect of quercetin on infarct size limiting in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Patients (n = 143) with first anterior STEMI within 6 hours from symptoms onset were included in this open-label multicenter pilot study. Patients were randomized either into quercetin group (n = 70) in addition to standard treatment or recommended therapy alone group (control group, n = 73). Quercetin infusions were initiated before reperfusion and repeated during the next 5 days. The infarct size assessed using creatine kinase-myocardial band area under curve (CK-MB AUC) was the primary study outcome. RESULTS: The study arms did not differ in demographics, time to admission, and main clinical data. The median early CK-MB AUC was significantly lower in quercetin group than in controls (8036 ± 7594 vs 11219 ± 8146 U × 1 h/L, p = 0.015). Intravenous quercetin administration was associated with less reperfusion-induced intramyocardial hemorrhage by Cardiac Magnetic Resonance on Day 3 (11.1% of patients in quercetin group vs 53.3% of patients in control group, p < 0.024). There were no significant differences in left ventricle ejection fraction and LV remodeling indicators. CONCLUSION: Our pilot study is the first to demonstrate novel insight into ischemia/reperfusion damage in STEMI patients. The addition of quercetin to standard STEMI therapy limits infarct size and prevents intramyocardial hemorrhage after the first anterior STEMI. Further research will be necessary to both validate and expand upon these findings.
Subject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Quercetin/therapeutic use , Pilot Projects , ST Elevation Myocardial Infarction/therapy , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Hemorrhage , Treatment OutcomeABSTRACT
Background: This study used late gadolinium enhancement-cardiac magnetic resonance (LGE-CMR) to assess myocardial infarct size, with the data being employed to predict whether patients with ischemic cardiomyopathy (ICM) would experience improvements in left ventricular function at 6 months following coronary artery bypass grafting (CABG). Methods: The data of patients with ICM with left ventricular ejection fraction (LVEF) ≤40% who underwent CABG were retrospectively analyzed. All patients underwent preoperative LGE-CMR imaging. Echocardiography results from 6 months post-CABG were used to assess improvements in LVEF, with improvement being defined as ΔLVEF ≥5%. The value of myocardial infarction segments and infarct size as predictors of improved cardiac function following CABG was analyzed. Results: Of the included patients, 66.7% (52/78) exhibited improved cardiac function at 6 months post-CABG. LGE-CMR imaging data revealed that compared to improved group, the improved group had significantly more myocardial infarct segments [improved group: median 1.0, interquartile range (IQR) 0-3; nonimproved group: median 4.0, IQR 3.0-6.0; P<0.001] and significantly greater myocardial infarct size (improved group: 22.4%±8.2%; nonimproved group: 34.7%±5.9%; P<0.001). The area under the receive operating characteristic curve values for myocardial infarct size in predicting cardiac function improvement were significantly higher than those of myocardial infarct segments (0.88 vs. 0.81; P=0.041). The respective sensitivity and specificity values for using a myocardial infarct size cutoff of 26.4% in differentiating between these 2 patient groups were 92.3% and 71.2%, respectively. According to logistic regression analysis, myocardial infarct size was an independent predictor of nonimprovement in cardiac function [odds ratio (OR) =1.244; 95% confidence interval (CI): 1.114-1.389; P<0.001]. A median 1.6-year follow-up interval (range, 0.5-4.1 years) revealed that the incidences of major adverse cerebrovascular events and cardiovascular events were significantly higher in the nonimproved group (5.8% vs. 26.9%; P<0.001), with these individuals having a higher New York Heart Association grading than patients with improved cardiac function (P=0.019). Conclusions: Myocardial infarct size can be measured to reliably predict improvements in cardiac function in patients with ICM following CABG. These results can guide clinicians in their efforts to identify those patients most likely to achieve positive outcomes following CABG.
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The present review summarizes the beneficial and detrimental roles of reactive oxygen species in myocardial ischemia/reperfusion injury and cardioprotection. In the first part, the continued need for cardioprotection beyond that by rapid reperfusion of acute myocardial infarction is emphasized. Then, pathomechanisms of myocardial ischemia/reperfusion to the myocardium and the coronary circulation and the different modes of cell death in myocardial infarction are characterized. Different mechanical and pharmacological interventions to protect the ischemic/reperfused myocardium in elective percutaneous coronary interventions and coronary artery bypass grafting, in acute myocardial infarction and in cardiotoxicity from cancer therapy are detailed. The second part keeps the focus on ROS providing a comprehensive overview of molecular and cellular mechanisms involved in ischemia/reperfusion injury. Starting from mitochondria as the main sources and targets of ROS in ischemic/reperfused myocardium, a complex network of cellular and extracellular processes is discussed, including relationships with Ca2+ homeostasis, thiol group redox balance, hydrogen sulfide modulation, cross-talk with NAPDH oxidases, exosomes, cytokines and growth factors. While mechanistic insights are needed to improve our current therapeutic approaches, advancements in knowledge of ROS-mediated processes indicate that detrimental facets of oxidative stress are opposed by ROS requirement for physiological and protective reactions. This inevitable contrast is likely to underlie unsuccessful clinical trials and limits the development of novel cardioprotective interventions simply based upon ROS removal.
Subject(s)
Myocardial Infarction , Myocardial Reperfusion Injury , Humans , Reactive Oxygen Species/metabolism , Myocardium/metabolism , Myocardial Infarction/metabolism , Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion Injury/metabolism , Oxidation-ReductionABSTRACT
OBJECTIVE: Obesity is a global health problem that increases the risk of coronary artery disease (CAD). However in studies, it has been observed that when the disease develops, obese patients have a more favorable prognosis than leaner patients. This is called the "obesity paradox." This study aims to evaluate the effect of obesity assessed with body fat percentage (BFP) and relative fat mass (RFM) besides body mass index (BMI) on infarct size (IS) estimated from peak creatine kinase-MB (CK-MB) levels in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: Patients with a diagnosis of NSTEMI who underwent coronary angiography between January 2017 and January 2022 were retrospectively evaluated. Patients without available anthropometric data to calculate BMI, BFP, and RFM and serial CK-MB measurements were excluded from the study. BMI was calculated using weight(kg)/(height[m])2 formula. Patients were dichotomized as obese (BMI≥30 kg/m2) and non-obese (BMI<30 kg/m2) to compare baseline characteristics. BFP and RFM were calculated from anthropometric data. Linear regression analysis was performed to define predictors of IS. RESULTS: Final study population consisted of 748 NSTEMI patients (mean age was 59.3±11.2 years, 76.3% were men, 36.1% of the patients were obese). Obese patients were more likely to be female, hypertensive, and diabetic. Smoking was less frequently observed in obese patients. Peak CK-MB levels were similar among groups. Obese patients had higher in-hospital left ventricular ejection fraction, and less severe CAD was observed in coronary angiographies of these patients. Multivariable regression analysis identified diabetes mellitus, systolic blood pressure, white blood cell count, hemoglobin, and BFP (ß=-4.8, 95% CI=-8.7; -0.3, p=0.03) as independent predictors of IS. CONCLUSION: Higher BFP is associated with smaller IS in NSTEMI patients. These findings support the obesity paradox in this patient group, but further, randomized controlled studies are required.
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BACKGROUND: Despite treatment with primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI), the risk of heart failure and late death remains high. Microvascular dysfunction, as assessed by the index of microcirculatory resistance (IMR), after primary PCI for STEMI has been associated with worse outcomes. It is unclear whether IMR after primary PCI predicts cardiac death. OBJECTIVES: The aims of this analysis were: 1) to determine if IMR is an independent predictor of cardiac death; 2) to assess the optimal cutoff value of IMR after STEMI; and 3) to compare IMR with several cardiac magnetic resonance parameters, including infarct size. METHODS: In a collaborative, pooled analysis of individual patient data from 6 cohorts that measured IMR directly after primary PCI, cardiac mortality up to 5 years was estimated using Kaplan-Meier analyses. The primary endpoint was cardiac death using the predefined IMR cutoff value of 40. RESULTS: In total, 1,265 patients were included in this study with a median follow-up of 2.8 years (IQR: 1.2-5.0 years). Cardiac death at 5 years occurred in 2.2% and 4.9% of patients (HR: 2.81; 95% CI: 1.34-5.88; P = 0.006) in the IMR ≤40 and IMR >40 groups, respectively. The composite of cardiac death or hospitalization for heart failure occurred in 4.9% and 8.9% (HR: 1.98; 95% CI: 1.20-3.29; P = 0.008) in the IMR ≤40 and IMR >40 groups, respectively. IMR was an independent predictor of cardiac death, whereas coronary flow reserve was not. The optimal cutoff value of IMR for the prediction of cardiac death in this cohort was 70 (HR: 4.73; 95% CI: 2.27-9.83; P < 0.001). Infarct size was 17.6% ± 13.3% and 23.9% ± 14.6% of the left ventricular mass in the IMR ≤40 and IMR >40 groups, respectively (P < 0.001). Microvascular obstruction and intramyocardial hemorrhage occurred more frequently in the IMR >40 group than in the IMR ≤40 group. CONCLUSIONS: In this large, pooled analysis of individual patient data, IMR measured directly after primary PCI in STEMI was an independent predictor of cardiac death. IMR may be used as a tool to identify patients at the time of primary PCI who are at highest risk for late cardiac mortality and who might benefit most from additional cardioprotective therapies and monitoring.
Subject(s)
Heart Failure , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Percutaneous Coronary Intervention/adverse effects , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/etiology , Microcirculation , Treatment Outcome , Heart Failure/therapy , Heart Failure/etiology , Death , Coronary CirculationABSTRACT
Ischemic postconditioning (IPoC) is a technique suggested to reduce reperfusion injury in patients suffering acute ST-elevation myocardial infarction (STEMI), although its use is highly controversial. This meta-analysis aimed to evaluate the effect of IPoC with percutaneous coronary intervention in patients with acute STEMI, as measured by follow-up left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging. The investigators searched PubMed, Embase, and Web of Science for all randomized controlled trials published during the last 2 decades. After the removal of duplicates, 2,021 articles from online databases had been identified using relevant search criteria. The included randomized controlled trials had studied patients with acute STEMI and Thrombolysis in Myocardial Infarction flow 0 to 1 at presentation and had measured follow-up LVEF using cardiac magnetic resonance imaging. Overall, 11 studies (n = 1,339 patients) qualified for inclusion. In each study, the control group did not differ significantly from the experimental group. The pooled data from included studies were analyzed using standardized mean difference between IPoC and control groups, and the 95% confidence interval for LVEF; the results were visualized using a forest plot. Bivariate regression analyses and 1-way analyses of LVEF coefficient ratios were done to isolate for various clinical and procedural parameters. An analysis of pooled data of the IPoC (n = 674) and control (n = 665) groups showed that IPoC did not significantly impact follow-up LVEF (using standardized mean difference 0.10, 95% confidence interval 0.00 to 0.21). Further analysis showed that IPoC did not improve follow-up LVEF when isolating for relevant clinical and procedural parameters. In conclusion, the use of IPoC as an adjunctive therapy to percutaneous coronary intervention seemingly provides no benefit to left ventricular systolic function, as quantified with cardiac magnetic resonance imaging, in patients with acute STEMI with Thrombolysis in Myocardial Infarction flow 0 to 1.
Subject(s)
Anterior Wall Myocardial Infarction , Ischemic Postconditioning , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , Ventricular Function, Left , Stroke Volume , Myocardium/pathology , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Ischemic Postconditioning/methods , Treatment Outcome , Myocardial Infarction/therapy , Magnetic Resonance ImagingABSTRACT
Reduced nitric oxide (NO) bioactivity in red blood cells (RBCs) is critical for augmented myocardial ischemia-reperfusion injury in type 2 diabetes. This study identified the nature of "NO bioactivity" by stimulating the intracellular NO receptor soluble guanylyl cyclase (sGC) in RBCs. sGC stimulation in RBCs from patients with type 2 diabetes increased export of cyclic guanosine monophosphate from RBCs and activated cardiac protein kinase G, thereby attenuating ischemia-reperfusion injury. These results provide novel insight into RBC signaling by identifying cyclic guanosine monophosphate from RBC as a mediator of protection against cardiac ischemia-reperfusion injury induced by sGC stimulation in RBCs.