Preventive impact of probiotic supplements on heart injury and inflammatory indices in a rat model of myocardial infarction: histopathological and gene expression evaluation.

Although there is a bulk of evidence on the favorable effect of probiotics on the cardiac system, their role in the management of myocardial infarction is not clear. Three viable probiotic bacterial strains, namely Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium lactis, were gavaged to the rats daily for 28 days prior to the induction of myocardial injury. Myocardial injury was induced by the use of isoproterenol (ISO) in the probiotics, control and sham groups. The heart tissues were catheterized to evaluate the histopathological parameters and measure the expression of genes related to inflammation. Treatment with ISO caused subendocardial necrosis and rupture of cardiac myofibrils. Pretreatment with probiotics reduced the size of myocardial infarction caused by ISO. Also, in the probiotic group, a relative decrease in the amount of tissue fibrosis and rupture of cardiomyocytes fibers was seen. Pretreatment with probiotics partially ameliorated myocardial necrosis, edema and leukocyte infiltration. Also, a remarkable decrease was detected in the expression of tissue proinflammatory genes in the pretreated group with probiotics. Thus, viable probiotic supplementation may ameliorate or prevent cardiac injury. Additional preclinical and clinical studies are required to clarify the impact of probiotics in the prevention and management of cardiovascular disease.

Effect of phosphatase and tensin homolog-induced putative kinase 1/ E3 ubiquitin ligase Parkin mediated mitochondrial autophagy on chronic kidney disease myocardial injury and the intervention mechanism of Shenshuai recipe.

OBJECTIVE: To study whether Shenshuai recipe (, SSR) can play a protective role on chronic kidney disease myocardial injury model through phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/E3 ubiquitin ligase Parkin (Parkin) mitochondrial autophagy pathway. METHODS: Forty-eight nephrectomized rats were randomly divided into six groups: sham-operated group, model group, Benazepril group, low, medium and high-dose groups of SSR. The rats were given the cor-responding intervention for six weeks, then were sacrificed. Serum was examined by enzyme linked immunosorbent assay (ELISA). Cardiac ultrasound was used to detect cardiac function in 5/6 nephrectomized rats. Myocardial tissue was examined by light and electron microscopy; PINK1, Parkin, microtubule-associated protein1 light chain 3 II (LC3B), sequestosome 1 (P62), BECN1 (Beclin-1) and dynamin-related protein 1 (Drp-1) were measured by real time polymerase chain reaction (RT-PCR), Western blot (WB) and immunohistochemistry (IHC). RESULTS: The expression levels of blood urea nitrogen (BUN) and creatinine (SCr) in the model group were significantly higher than those in the sham-operated group, indicating that modeling was successful. SSR can protect myocardium by reducing the relative expression of creatine kinase myocardial isoenzyme and hypersensitivity cardiac troponin I (P<0.05). SSR can improve cardiac function in rats after ultrasound testing. SSR can improve the pathological manifestations of myocardial tissue after Masson staining. SSR can increase the number of autophagosomes and autophagiclysosomes in 5/6 nephrectomized rats (P<0.05). Determined by RT-PCR, WB and IHC, SSR can increase the relative expression of PINK1, Parkin, and LC3B (P<0.05), and decrease the relative expression of P62, Beclin-1 and Drp-1 (P<0.05). CONCLUSIONS: The PINK1/Parkin mitochondrial autophagy pathway in myocardial tissues in 5/6 nephrectomy CKD myocardial injury rats was inhibited. SSR can activate PINK1/Parkin mitochondrial autophagy to enhance mitochondrial autophagy, and play a protective role in myocardial tissues.

Effect of dexmedetomidine on postoperative high-sensitivity cardiac troponin T in patients undergoing video-assisted thoracoscopic surgery: a prospective, randomised controlled trial.

BACKGROUND: One-lung ventilation and intrathoracic operations during thoracoscopic surgery often result in intraoperative hypoxaemia and haemodynamic fluctuations, resulting in perioperative myocardial injury. Dexmedetomidine, an alpha-2 (α-2) agonist, has demonstrated myocardial protection. We hypothesize that the routine intravenous administration of dexmedetomidine could reduce the extent of myocardial injury during video-assisted thoracoscopic surgery (VATS). METHODS: The study included patients aged ≥ 45 years, classified as American Society of Anesthesiologists physical status I-III, who underwent general anesthesia for video-assisted thoracoscopic surgery. The patients were randomly assigned to either the intervention group, receiving general anesthesia with dexmedetomidine, or the control group, receiving general anesthesia without dexmedetomidine. Patients in the intervention group received a loading dose of dexmedetomidine (0.5 µg·kg-1) before anesthesia induction, followed by a continuous infusion (0.5 µg·kg-1·h-1) until the completion of the surgery. Placebos (saline) were administered for the control group to match the treatment. The primary outcome assessed was the high-sensitivity cardiac troponin T on postoperative day 1. Additionally, the incidence of myocardial injury after noncardiac surgery (MINS) was noted. RESULTS: A total of 110 participants completed this study. The median [interquartile range (IQR)] concentration of hs-cTnT on postoperative day 1 was lower in the intervention group compared with the control group (7 [6-9] vs. 8 [7-11] pg·ml-1; difference in medians,1 pg·ml-1; 95% confidence interval [CI], 0 to 2; P = 0.005). Similarly, on postoperative day 3, the median [IQR] concentration of hs-cTnT in the intervention group was also lower than that in the control group (6 [5-7] vs. 7 [6-9]; difference in medians,1 pg·ml-1; 95%CI, 0 to 2; P = 0.011). Although the incidence of MINS was not statistically significant (the intervention group vs. the control group, 3.8% vs. 9.1%, P = 0.465), there was a decreasing trend in the incidence of MINS in the intervention group. CONCLUSION: The administration of perioperative dexmedetomidine in patients ≥ 45 years undergoing video-assisted thoracoscopic surgery could lower the release of postoperative hs-cTnT without reducing incidence of myocardial injury. TRIAL REGISTRATION: chictr.org.cn (ChiCTR2200063193); prospectively registered 1 September 2022.

Development of an Extended Cardiovascular SOFA Score Component Reflecting Cardiac Dysfunction with Improved Survival Prediction in Sepsis: An Exploratory Analysis in the Sepsis and Elevated Troponin (SET) Study.

INTRODUCTION: The cardiovascular component of the Sequential Organ Failure Assessment (SOFA) score does not correspond with contemporary clinical practice in sepsis or identify impaired cardiac function. Our aim was to develop a modified cardiovascular SOFA component that reflects cardiac dysfunction and improves the SOFA score's 30-day mortality discrimination. METHODS: A cohort of sepsis patients from a previous study was divided into a training (n = 250) and test cohort (n = 253). Nine widely available measures of cardiovascular function were screened for association with 30-day mortality using natural cubic spline. High-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro B-type natriuretic peptide (NT-proBNP) and heart rate (HR) were transformed into ordinal variables (0-4 points). The presence of atrial fibrillation (AF) was assigned two points. The SOFA score was extended by adding the variable points in different weights and combinations. The best-performing cardiac-extended model (CE-SOFA) was evaluated in the test cohort. Improved prognostic discrimination and calibration were assessed using logistic regression, area under receiver operating characteristic curves (AUC), Net Reclassification Improvement (NRI) index, and DeLong and Hoshmer-Lemeshow tests. RESULTS: In the training cohort, all differently weighted and combined models using hs-cTnT, NT-proBNP and AF points added to the SOFA score showed improved discriminative ability (AUC 0.67-0.75) compared to the SOFA score (AUC 0.62; NRI P < .001; DeLong P ≤ .001). In the test cohort, CE-SOFA demonstrated improved 30-day mortality discrimination compared to the SOFA score (AUC 0.72 vs 0.68), exhibiting good calibration and significantly improved discrimination using the NRI index (P = .009) but not the DeLong test (P = .142). CONCLUSIONS: The CE-SOFA model reflects cardiac dysfunction and improves 30-day mortality discrimination in sepsis. External validation is the next step to further substantiate a revised cardiovascular component in a future SOFA 2.0.

Machine-Learning for Phenotyping and Prognostication of Myocardial Infarction and Injury in Suspected Acute Coronary Syndrome.

Background: Clinical work-up for suspected acute coronary syndrome (ACS) is resource intensive. Objectives: This study aimed to develop a machine learning model for digitally phenotyping myocardial injury and infarction and predict 30-day events in suspected ACS patients. Methods: Training and testing data sets, predominantly derived from electronic health records, included suspected ACS patients presenting to 6 and 26 South Australian hospitals, respectively. All index presentations and 30-day death and myocardial infarction (MI) were adjudicated using the Fourth Universal Definition of MI. We developed 2 diagnostic prediction models which phenotype myocardial injury and infarction according to the Fourth UDMI (chronic myocardial injury vs acute myocardial injury patterns, the latter further differentiated into acute non-ischaemic myocardial injury, Types 1 and 2 MI) using eXtreme Gradient Boosting (XGB) and deep-learning (DL). We also developed an event prediction model for risk prediction of 30-day death or MI using XGB. Analyses were performed in Python 3.6. Results: The training and testing data sets had 6,722 and 8,869 participants, respectively. The diagnostic prediction XGB and deep learning models achieved an area under the curve of 99.2% ± 0.1% and 98.8% ± 0.2%, respectively, for differentiating an acute myocardial injury pattern from no injury or chronic myocardial injury pattern and achieved 95.5% ± 0.2% and 94.6% ± 0.9%, respectively, for differentiating type 1 MI from type 2 MI or acute nonischemic myocardial injury. The 30-day death/MI event prediction model achieved an area under the curve of 88.5% ± 0.5%. Conclusions: Machine learning models can digitally phenotype suspected ACS patients at index presentation and predict subsequent events within 30 days. These models require external validation in a randomized clinical trial to evaluate their impact in clinical practice.

LncRNA ZFAS1/miR-186-5p axis is involved in oxidative stress inhibition of myocardial ischemia-reperfusion injury by targeting BTG2.

OBJECTIVE: To probe the involvement of long noncoding RNA zinc finger antisense 1 (ZFAS1)/microRNA (miR)-186-5p axis in inhibiting oxidative stress in myocardial ischemia-reperfusion injury (MIRI) by targeting B-cell translocation gene 2 (BTG2). METHODS: The MIRI mice model was established by ligating the left anterior descending branch of the left coronary artery in C57BL/6 mice. The in vitro MIRI model was constructed by hypoxia and reoxygenation of HL-1 cardiomyocytes. Cardiomyocyte apoptosis and the extent of myocardial injury in mice were detected. The apoptosis rates, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in HL-1 cells were assessed. The relationship among ZFAS1, miR-186-5p, and BTG2 was verified. RESULTS: High ZFAS1 and BTG2 levels and low miR-186-5p levels were demonstrated in I/R-injured myocardial tissues and in H/R-treated cardiomyocytes. Interference with ZFAS1 or elevation of miR-186-5p inhibited apoptosis and oxidative stress in H/R model cardiomyocytes and I/R-injured myocardial tissues. Overexpressing BTG2 impaired the ameliorative effects of miR-186-5p on MIRI. ZFAS1 negatively regulated miR-186-5p expression by acting as a molecular sponge. miR-186-5p targeted to regulate BTG2 negatively. CONCLUSION: Interfering with ZFAS1 can upregulate miR-186-5p and thus inhibit BTG2 expression, thereby ameliorating MIRI.

Immune-response gene 1 deficiency aggravates inflammation-triggered cardiac dysfunction by inducing M1 macrophage polarization and aggravating Ly6Chigh monocyte recruitment.

The immune response gene 1 (IRG1) and its metabolite itaconate are implicated in modulating inflammation and oxidative stress, with potential relevance to sepsis-induced myocardial dysfunction (SIMD). This study investigates their roles in SIMD using both in vivo and in vitro models. Mice were subjected to lipopolysaccharide (LPS)-induced sepsis, and cardiac function was assessed in IRG1 knockout (IRG1-/-) and wild-type mice. Exogenous 4-octyl itaconate (4-OI) supplementation was also examined for its protective effects. In vitro, bone marrow-derived macrophages and RAW264.7 cells were treated with 4-OI following Nuclear factor, erythroid 2 like 2 (NRF2)-small interfering RNA administration to elucidate the underlying mechanisms. Our results indicate that IRG1 deficiency exacerbates myocardial injury during sepsis, while 4-OI administration preserves cardiac function and reduces inflammation. Mechanistic insights reveal that 4-OI activates the NRF2/HO-1 pathway, promoting macrophage polarization and attenuating inflammation. These findings underscore the protective role of the IRG1/itaconate axis in SIMD and suggest a therapeutic potential for 4-OI in modulating macrophage responses.

Novel troponin fragmentation assay to discriminate between Takotsubo syndrome and acute myocardial infarction.

BACKGROUND: Cardiac troponin levels are elevated in Takotsubo syndrome (TTS) with significant overlap to acute myocardial infarction (MI). Long and intact cardiac troponin T (cTnT) forms are typical for MI. This study sought to assess whether the fragmentation composition of cTnT release in TTS differs from MI. METHODS: The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence immunoassay and total cTnT with a commercial high-sensitivity cTnT assay in 24 TTS patients and in 84 Type 1 MI patients. The ratio of long to total cTnT (troponin ratio) was determined as a measure of cTnT fragmentation. RESULTS: Troponin ratio was lower in TTS patients 0.13 [0.10-0.20] vs. 0.62 [0.29-0.96], p<0.001). In the ROC curve analyses, troponin ratio showed a better predictive power than total cTnT in discriminating TTS and MI patients (AUC 0.869 [CI95% 0.789-0.948)] vs. 0.766 [CI95% 0.677-0.855], p=0.047). When restricting the analysis to patients with total cTnT below 1200 ng/L (maximal value in TTS patients), the respective AUC values for total cTnT and troponin ratio were 0.599 (CI 95% 0.465-0.732) and 0.816 (CI95% 0.712-0.921), p =0.003). At a cutoff point of 0.12, troponin ratio correctly identified 95% of MI patients and 50% of TTS patients. CONCLUSIONS: In contrast to Type 1 MI, only a small fraction of circulating cTnT in TTS exists in intact or long molecular forms. This clear difference in troponin composition could be of diagnostic value when evaluating patients with cTnT elevations and suspicion of TTS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465591.

Colchicine prevents perioperative myocardial injury in cardiac surgery by inhibiting the formation of neutrophil extracellular traps: evidence from rat models.

OBJECTIVES: Colchicine, an anti-inflammatory agent, has been reported to improve myocardial infarction prognosis by inhibiting neutrophil extracellular traps (NETs) release. However, its role in cardiac surgery and the mechanisms behind NETs suppression remain unclear. This study aimed to explore colchicine's cardioprotective effects against perioperative myocardial injury in cardiac surgery, focusing on NETs inhibition as a novel therapeutic strategy. METHODS: Male Sprague-Dawley rats were pre-treated with colchicine (0.1 mg/kg/day) or CI-amidine (10 mg/kg/day) for 7 days before undergoing cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. The model was created by subjecting the rats to cardiopulmonary bypass and myocardial ischaemia/reperfusion injury. Under 4.0% sevoflurane anaesthesia, cardiopulmonary bypass was initiated by cannulating the tail artery and right atrium, and perfusion was maintained for 4 h. Immunofluorescence detected NETs, and haematoxylin and eosin staining assessed inflammatory cell. RESULTS: We found colchicine treatment significantly reduced perioperative myocardial injury in rats. Furthermore, we observed a notable elevation of NETs in the myocardial tissue of animal models. Moreover, suppressing peptidylarginine deiminase 4 was found to markedly diminish perioperative myocardial injury in rats. Additionally, colchicine can mitigate the release of NETs by inhibiting peptidylarginine deiminase 4. CONCLUSIONS: NETs were significantly elevated during the perioperative period of cardiac surgery. Colchicine significantly mitigated myocardial injury in cardiac surgery by inhibiting NETs formation, with peptidylarginine deiminase 4 inhibition being one of its mechanisms.

Coronary Computed Tomography Angiography (CTA) Findings in COVID-19.

(1) Background: The novel SARS-CoV-2 virus infects the endothelium. Vasculitis may lead to specific coronary artery wall lesions. Coronary computed tomography angiography (CTA) imaging findings have not been systematically reported. The aim of this study was to describe a case series using CTA. (2) Methods: Patients with recent RT-PCR confirmed SARS-CoV-2 infection referred for coronary CTA for clinical indications (e.g., chest pain, troponin+, and ECG abnormalities) were included. Coronary CTA findings, such as atypical coronary lesions suggestive of vasculitis, perivascular inflammation measured by using pericoronary fat attenuation (PCAT) index, coronary artery disease, and extracoronary findings were collected. (3) Results: Results for 12 patients (54.8 ± 22 years; four females) with SARS-CoV-2 infection within 60 days (four acute care and eight stable patients) are reported. Time to positive RT-PCR was a mean of 15.1 days (range, 0-51). In four acute patients with signs of myocardial injury, plaque rupture (n = 1), hyperenhancing myocardium/MINOCA (n = 1), MINOCA (n = 1), and pericarditis with acute heart failure (LVEF 20%) (n = 1) were found. All (100%) had pericardial effusion and signs of perivascular inflammation. Among eight stable patients, pericardial effusion or perivascular inflammation were found in only two (25%). Coronary artery disease was ruled out in five (62.5%) (4) Conclusions: Coronary CTA is a useful imaging modality in the diagnostic work up of patients with COVID-19 infection, and is able to describe coronary and other cardiac abnormalities.

Nppb contributes to Sepsis-Induced myocardial injury by regulating Senescence-Related genes.

BACKGROUND: Sepsis, a systemic inflammatory condition, is a leading cause of mortality due to cardiovascular injury. Sepsis and cellular senescence are closely related, yet the specific mechanisms are still unclear. This study aims to identify a novel therapeutic target for mitigating sepsis-induced myocardial injury. METHODS: We initially assessed serum inflammatory markers and myocardial injury indicators in septic mice. This involved observing inflammatory cell infiltration in ventricular muscle tissue, assessing cardiac function, and recording electrocardiograms. We examined the expression of connexin 40 (Cx40) and connexin 43 (Cx43) and analyzed mitochondrial structures in ventricular tissues. A conditional heart-specific Nppb knockout mouse model was then developed in mice to evaluate these changes. Ventricular tissues were analyzed via mRNA sequencing to identify differentially expressed genes (DEGs), which were cross-referenced with senescence-related genes to identify key hub genes. The expression and distribution of hub genes were subsequently analyzed by single-cell analysis. Finally, the expression of the senescence-related gene CCL2, along with cardiac structure and function, was validated in a conditional heart-specific Nppb knockout sepsis mouse model. RESULTS: Myocardial injury severity positively correlated with serum brain natriuretic peptide (BNP) in septic mice. Conditional heart-specific Nppb knockout improved myocardial injury outcomes in mice with sepsis. The DEGs identified in the conditional heart-specific Nppb knockout model overlapped with senescence-related genes, identifying seven upregulated genes associated with inflammation, cardiac contraction and apoptotic pathways. Single-cell analysis confirmed high CCL2 levels and an increased macrophage presence correlating with sepsis progression. Conditional heart-specific Nppb knockout reduced CCL2 levels, which were associated with improved cardiac structure and function. CONCLUSION: This study confirms that conditional heart-specific Nppb knockout reduces CCL2 expression, thereby ameliorating myocardial injury in septic mice. Targeting Nppb to regulate the senescence-related gene CCL2 may represent an effective strategy for treating myocardial injury in septic patients.

Association Between Family Income, Subclinical Myocardial Injury, and Cardiovascular Mortality in the General Population.

INTRODUCTION: Both low family income and subclinical myocardial injury (SCMI) are risk factors for cardiovascular disease (CVD) mortality. However, the impact of their joint association on CVD mortality is unclear. METHODS: This analysis from the third National Health and Nutrition Examination Survey included 6805 participants (age 59.1 ± 13.4 years, 52.3% women, and 49.8% White) free of CVD at baseline. Family income was assessed using the poverty-income ratio (PIR) and categorized into low (PIR < 1), middle (PIR = 1-4), and high (PIR > 4) income. A validated ECG-based cardiac infarction injury score (CIIS) ≥ 10 was considered positive for SCMI. CVD mortality was determined using the National Death Index. Cox-proportional hazard analysis was used to evaluate the associations of family income and SCMI, separately and jointly, with CVD mortality. RESULTS: A total of 1782 (26.2%) participants had SCMI at baseline. During a median follow-up of 18.2 years, 856 (12.6%) events of CVD mortality occurred. In separate multivariable Cox models, SCMI (vs. no SCMI) and middle- and low-income (vs. high-income) were each associated with a higher risk of CVD mortality (HR [95% CI]: 1.34 [1.16-1.54], 1.44 [1.16-1.78], and 1.59 [1.22-2.07], respectively). Compared to high-income participants without SCMI, those with low-income and SCMI had an increased risk of CVD mortality (HR [95% CI]: 2.17 [1.53-3.08]). The multiplicative interaction between PIR and SCMI was not significant (p = 0.054). CONCLUSION: Lower family income and SCMI are associated with CVD mortality, and their concomitant presence is associated with the highest risk. Family income and SCMI may help in the individualized assessment of CVD risk.

Mitochondrial Stress as a Central Player in the Pathogenesis of Hypoxia-Related Myocardial Dysfunction: New Insights.

Hypoxic injury is a critical pathological factor in the development of various cardiovascular diseases, such as congenital heart disease, myocardial infarction, and heart failure. Mitochondrial quality control is essential for protecting cardiomyocytes from hypoxic damage. Under hypoxic conditions, disruptions in mitochondrial homeostasis result in excessive reactive oxygen species (ROS) production, imbalances in mitochondrial dynamics, and initiate pathological processes including oxidative stress, inflammatory responses, and apoptosis. Targeted interventions to enhance mitochondrial quality control, such as coenzyme Q10 and statins, have shown promise in mitigating hypoxia-induced mitochondrial dysfunction. These treatments offer potential therapeutic strategies for hypoxia-related cardiovascular diseases by regulating mitochondrial fission and fusion, restoring mitochondrial biogenesis, reducing ROS production, and promoting mitophagy.

Noninvasive Left Ventricular Pressure-Strain Loop for Quantitative Assessment of Early Left Ventricular Systolic Dysfunction in Patients With Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) possess a pronounced risk for cardiovascular events. A noninvasive left ventricular pressure-strain loop (LV-PSL) has recently been introduced to detect subtler changes in cardiac function. This study aims to investigate the value of LV-PSL for quantitative assessment of myocardial work (MW) in patients with CKD. METHODS: Seventy-five patients with CKD were enrolled retrospectively (37 patients with CKD Stages 2-3, and 38 patients with CKD Stages 4-5), and 35 healthy volunteers were included as controls. All subjects underwent transthoracic echocardiography. LV-PSL analysis was performed to estimate LV MW and efficiency. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained by echocardiography, and the differences among the groups were compared. RESULTS: There was a significant increase in GWW and reduction in GWE in patients with CKD compared to normal controls (p < 0.05). No significant difference in GWI and GCW was observed among the three groups. Multiple linear regression revealed that increased GWW was significantly associated with age, serum creatinine, and systolic pressure, and decreased GWE was associated with age, serum creatinine, and GLS. CONCLUSION: LV-PSL can be used for noninvasive quantitative assessment of MW in patients with CKD, providing a new sensitive approach for the clinical assessment of myocardial function.

Cardiac troponin elevation and mortality in takotsubo syndrome: New insights from the international takotsubo registry.

BACKGROUND: The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS). METHODS: Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis. RESULTS: Out of 2'938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18-2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001). CONCLUSION: This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up.

Renin-Angiotensin System Inhibition in Patients With Myocardial Injury Complicating Transcatheter Aortic Valve Replacement.

Background: Periprocedural myocardial injury impacts clinical outcome after transcatheter aortic valve replacement (TAVR). The optimal medical management strategy for TAVR-related periprocedural myocardial injury has not been established. Objectives: The authors aimed to investigate the prognostic association of renin-angiotensin system (RAS) inhibitors in patients with periprocedural myocardial injury after TAVR. Methods: In a prospective TAVR registry, patients were retrospectively stratified according to Valve Academic Research Consortium (VARC)-3 periprocedural myocardial injury and RAS inhibitor prescription after TAVR. The main outcomes of interest were prevalence of myocardial injury and cardiovascular death. Logistic and Cox proportional hazards regression were used to analyze outcomes of interest. Results: Among 2,083 eligible patients undergoing TAVR between August 2007 and June 2023, 283 patients (13.8%) developed VARC-3 periprocedural myocardial injury. RAS inhibitors were prescribed in 197 patients (70%) with periprocedural myocardial injury and in 1,251 patients (71.2%) without injury. Compared with patients without periprocedural myocardial injury, patients with myocardial injury had an increased risk of cardiovascular death at 1 year (HRadjusted: 2.08; 95% CI: 1.39-3.11). The use of RAS inhibitors after TAVR was associated with a reduced risk of cardiovascular death in patients with and without periprocedural myocardial injury (HRadjusted: 0.46; 95% CI: 0.22-0.95, and HRadjusted: 0.44; 95% CI: 0.30-0.65, respectively). Conclusions: One out of 7 patients undergoing TAVR experienced periprocedural myocardial injury. VARC-3 periprocedural myocardial injury was associated with a 2-fold increased risk of cardiovascular death at 1 year after TAVR. The favorable association of RAS inhibitor prescription was consistent in patients with and without periprocedural myocardial injury. (SwissTAVI Registry; NCT01368250).

Significance of detecting cardiac troponin I and creatine kinase MB in critically Ill children without primary cardiac illness.

Objective: To investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment. Methods: The serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared. Results: The incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P < 0.05). The single-elevated and normal groups only showed a difference in mortality (P < 0.017). The cTnI and CK-MB concentrations were negatively correlated with prognosis (P < 0.01). Conclusion: Myocardial injury, as evidenced by elevated cardiac biomarkers, is common in critically ill children without primary cardiac illness. cTnI and CK-MB are associated with outcomes. Shock, heart failure, and multiple organ dysfunction syndromes are independently associated with simultaneous elevations of CK-MB and cTnI concentrations. Further prospective studies are needed to elucidate the clinical utility of these biomarkers.

Characteristic Cardiac Magnetic Resonance (CMR) Imaging Findings of Cocaine-Induced Myocardial Injury.

Cocaine is a widely available illicit substance with a costly financial and social burden on the healthcare infrastructure. Both acute and chronic cocaine use can lead to sequelae of cardiac diseases, including myocardial infarction, aortic dissection, and cardiomyopathy. Cardiac magnetic resonance (CMR) imaging is a powerful tool for detecting myocardial injury leading to prompt treatment and risk stratification. We present two differing cases of sequelae of myocardial injury as a result of cocaine use. We present critical findings on CMR imaging, including myocardial injury patterns, which can help differentiate between acute and chronic injury and assess the extent of damage. Cocaine exerts potent sympathomimetic effects, increasing myocardial oxygen demand and causing coronary vasospasm, thrombosis, and direct myocyte toxicity. Acute cocaine use significantly elevates the risk of myocardial infarction, while chronic use can lead to cardiomyopathy and heart failure. CMR features include wall motion abnormalities, myocardial perfusion defects, and fibrosis. Early identification and intervention can potentially reverse interstitial fibrosis before progression to irreversible damage. CMR is an essential diagnostic tool for characterizing myocardial injury, distinguishing between reversible and irreversible damage, and providing prognostic information on cocaine-induced myocardial injury. The cases highlight the importance of CMR in managing and understanding the full spectrum of cocaine-related cardiac damage.