scholarly journals Clinical value and role of microRNA-29c-3p in sepsis-induced inflammation and cardiac dysfunction

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Bingyu Zhang ◽  
Lin Yu ◽  
Ying Sheng
Keyword(s):  
Inflammatory Response ◽  
Roc Curve ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Diastolic Pressure ◽  
Cecal Ligation ◽  
Systolic Pressure ◽  
Diagnostic Value ◽  
Left Ventricular ◽  
Tnf Α

Abstract Background The goal of this study was to investigate the diagnostic value of miR-29c-3p in sepsis and its role in sepsis-induced inflammatory response and cardiac dysfunction. Methods Serum level of miR-29c-3p was detected by qRT-PCR. The ROC curve was used to evaluate the diagnostic value of miR-29c-3p for Sepsis. The cecal ligation and puncture method (CLP) was used to establish a rat sepsis model. To assess cardiac function, left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dtmax) in different experimental groups were detected, and the serum cardiac troponin I (cTnI), creative kinase isoenzyme MB (CK-MB) were measured by ELISA. Meanwhile, TNF-α, IL-1β, and IL-6 were detected by ELISA to assess the level of inflammatory response in animals. Results miR-29c-3p level was upregulated in sepsis patients. ROC curve revealed that miR-29c-3p had the ability to distinguish sepsis patients from healthy controls. Cardiac dysfunction and inflammation were observed in sepsis rat, which were characterized by the decrease of LVSP and + dp/dtmax, the increase of LVEDP, − dp/dtmax, cTnI, CK-MB, TNF-α, IL-1β, IL-6. All effects were reversed by the injection of miR-29c-3p antagomir. Logistics regression analysis manifested miR-29c-3p is an independent factor in the occurrence of cardiac dysfunction in sepsis patients. Conclusions miR-29c-3p has potential as a biomarker for the diagnosis of sepsis, and inhibition of miR-29c-3p expression in animal models reduced sepsis-induced cardiac dysfunction and inflammatory response.

scholarly journals MicroRNA-495 serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation and cardiac dysfunction

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Hailei Guo ◽  
Liying Tang ◽  
Jianjun Xu ◽  
Cai Lin ◽  
Xiangwei Ling ◽  
...  
Keyword(s):  
Sofa Score ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Cecal Ligation ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Apache Ii Score ◽  
Diagnostic Biomarker ◽  
Blood Cytokines ◽  
Tnf Α

Abstract Background Sepsis leads to severe inflammatory and cardiac dysfunction. This study aimed to explore the clinical value of miR-495 in sepsis, as well as its role in sepsis-induced inflammation and cardiac dysfunction. Methods 105 sepsis patients were recruited; receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of miR-495 in sepsis. A model of sepsis in rats was created via performing cecal ligation and puncture (CLP). After modeling, the cardiac function, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dtmax), and serum cardiac troponin I (CTn-I), creative kinase isoenzyme MB (CK-MB) were detected. The blood cytokines levels including TNF-α, IL-6, IL-1β were also measured. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-495. Results MiR-495 was significantly downregulated in sepsis patients, especially patients who suffered from septic shock (SS). MiR-495 expression was negatively associated with Scr, WBC, CRP, PCT, APACHE II score and SOFA score. MiR-495 could distinguish patients with SS from non-SS patients. MiR-495 and SOFA score were better indictors for the occurrence of cardiac dysfunction in sepsis patients. In CLP-induced sepsis model. CLP rats experienced deterioration of LVSP, LVEDP, ± dp/dtmax, and had a rise in serum CTn-I, CK-MB, TNF-α, IL-6 and IL-1β, which were improved by miR-495 agomir injection. Conclusions MiR-495 might be a potential diagnostic biomarker for sepsis patients, and overexpression of miR-495 alleviated sepsis-induced inflammation and cardiac dysfunction.

Abstract 12624: Blockade of Exosome Secretion Attenuates Inflammatory Cytokines, Mitigates Cardiac Dysfunction, and Reduces Mortality in Polymicrobial Sepsis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Xiaohong Wang ◽  
Dongze Qin ◽  
Kobina Essandoh ◽  
Wei Huang ◽  
Liwang Yang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Cardiac Dysfunction ◽  
Contractile Function ◽  
Cecal Ligation ◽  
Left Ventricular ◽  
Polymicrobial Sepsis ◽  
Raw 264.7 Cells ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Tnf Α

Introduction: Exosomes, a group of nano-vesicles secreted from living cells, are documented to increase in the circulation and are believed to promote cardiac dysfunction in sepsis patients and animal models. However, whether inhibition of exosome release could exert a cardio-protective effect in polymicrobial sepsis remains unexplored. Methods and Results: C57BL/6 mice (male, 8-week old) were pre-treated with GW4869 (dissolved in DMSO, injection i.p. at a dose of 2.5μg/g body weight), a known inhibitor of exosome secretion. Same volume of DMSO was used as controls. One hour later, cecal ligation and puncture (CLP) surgery was performed to induce polymicrobial sepsis. We found that the concentration of serum exosomes, measured by membrane markers CD63 and CD81with detection ELISA kits, was increased by 3.5-fold in DMSO-CLP mice, but no increase was detected in GW4869-CLP mice or in sham operated mice (n=4-6, p<0.01). Myocardial contractile function, assessed at 12h post-CLP using a SONOS-7500 echocardiography system, revealed that pre-injection of GW4869 significantly attenuated CLP-associated cardiac dysfunction, evidenced by an improved left ventricular ejection fraction (LVEF) and minor axis fractional shortening (LVFS), compared to DMSO controls (n=8-10, p<0.01). Myeloperoxidase (MPO) activity, a marker of myocardial inflammation, measured with a [[Unable to Display Character: &#64258;]]uorometric assay kit, also showed a significant reduction in GW4869-pre-treated mice, compared to DMSO-controls (n=5, p<0.01). Similarly, serum levels of inflammatory cytokines TNF-α and IL-1β triggered by CLP were reduced by 72% and 61%, respectively in GW4869-treated mice, compared with controls (n=6). Furthermore, we observed that 67% (n=9) of the DMSO controls, but only 20% in GW4869-treated mice (n=10) had died by 48h post-CLP. In vitro study confirmed that GW4869 limited the production of TNF-α and IL-1β in RAW 264.7 cells (a mouse macrophage cell line) challenged with endotoxin (LPS, 1μg/ml, 24 h). Conclusions: Together, this study indicates that blockade of exosome secretion could attenuate the inflammatory cytokine response as well as the consequent cardiac dysfunction and mortality in polymicrobial sepsis. Thus, our study may provide a new approach to the treatment of sepsis.

Absence of meal-induced insulin sensitization (AMIS) in aging rats is associated with cardiac dysfunction that is protected by antioxidants

2011 ◽  
Vol 111 (3) ◽  
pp. 704-714 ◽  
Author(s):  
Zhi Ming ◽  
Dallas J. Legare ◽  
W. Wayne Lautt
Keyword(s):  
Cardiac Dysfunction ◽  
Insulin Action ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Cardiac Performance ◽  
Sprague Dawley ◽  
Antioxidant Treatment ◽  
Aging Rats ◽  
Progressive Development

We have previously demonstrated that progressive development of absence of meal-induced insulin sensitization (AMIS) leads to postprandial hyperglycemia, compensatory hyperinsulinemia, resultant hyperlipidemia, increased oxidative stress, and obesity, progressing to syndrome X in aging rats. The present study tested the hypothesis that progressive development of AMIS in aging rats further resulted in deterioration in cardiac performance. Anesthetized male Sprague-Dawley rats were tested at 9, 26, and 52 wk to determine their dynamic response to insulin and cardiac function. Dynamic insulin sensitivity was determined before and after atropine to quantitate hepatic insulin sensitizing substance (HISS)-dependent and -independent insulin action. Cardiac performance was evaluated using a Millar pressure-volume conductance catheter system. AMIS developed with age, as demonstrated by significant decrease in HISS-dependent insulin action, and this syndrome was increased by sucrose supplementation and inhibited by the antioxidant treatment. Associated with progressive development of AMIS, aging rats showed impaired cardiac performance, including the reduction in cardiac index, heart rate, dP/d tmax, dP/d tmin, ejection fraction and decreased slope of left ventricular end-systolic pressure-volume relationship, and increased relaxation time constant of left ventricular pressure as well as increased left ventricular end-diastolic pressure. Total peripheral vascular resistance also increased with age. Sucrose supplementation and antioxidant treatment, respectively, potentiated and attenuated cardiac dysfunction associated with age. In addition, poor cardiac performance correlated closely with the development of AMIS. These results indicate that AMIS is the first metabolic defect that leads to homeostatic disturbances and dysfunctions, including cardiovascular diseases.

scholarly journals Long-Term Administration of Neuropeptide Y in the Subcutaneous Infusion Results in Cardiac Dysfunction and Hypertrophy in Rats

2015 ◽  
Vol 37 (1) ◽  
pp. 94-104 ◽  
Author(s):  
Rong Zhang ◽  
Huifang Niu ◽  
Xiaohui Kang ◽  
Tao Ban ◽  
Hong Hong ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Cardiac Remodeling ◽  
Cardiac Dysfunction ◽  
Diastolic Pressure ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Mitogen Activated Protein Kinase ◽  
Elevated Plasma

Background/Aims: The purpose of the present study was to clarify whether chronically elevated plasma neuropeptide Y (NPY) might affect heart function and cardiac remodeling in rats. Methods: Male Wistar rats were administered NPY (85 μg for 30 days) by mini-osmotic pump subcutaneously implanted between the scapulae. Associated indices for heart function, cardiac remodeling and hypertrophy were evaluated. Results: Compared to the sham group, the baseline systolic blood pressure (SBP) in rats administered NPY was significantly increased; cardiac function was significantly decreased, as indicated by reduced ejection fraction (EF), left ventricular end-systolic pressure (LVESP), maximum change velocity of left ventricular pressure in the isovolumic contraction or relaxation period (±dp/dtmax) and increased left ventricular end-diastolic pressure (LVEDP); hematoxylin-eosin (H&E) staining detection displayed enlarged cell areas and a consistent increase in heart-to-body weight ratios (HW/BW) was observed; quantitative real time PCR (qRT-PCR) and Western blot analysis showed markedly increased expressions of β-myosin heavy chain (β-MHC), calcineurin (CaN) and phosphorylated p38 proteins, while no changes were found in the expressions of p38 total protein and the phosphorylations of JNK and ERK. Conclusion: This study reported for the first time that long-term elevated plasma concentration of NPY could induce cardiac dysfunction and cardiac hypertrophy and this phenomenon could, in part, be mediated by the Ca2+/CaM-dependent CaN pathway and p38 mitogen-activated protein kinase (MAPK) signal pathway in rats.

scholarly journals Naive Rat Amnion-Derived Cell Transplantation Improved Left Ventricular Function and Reduced Myocardial Scar of Postinfarcted Heart

2009 ◽  
Vol 18 (4) ◽  
pp. 477-486 ◽  
Author(s):  
Kazuro L. Fujimoto ◽  
Toshio Miki ◽  
Li J. Liu ◽  
Ryotaro Hashizume ◽  
Stephen C. Strom ◽  
...  
Keyword(s):  
Stem Cell ◽  
Troponin I ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Smooth Muscle Actin ◽  
Embryonic Stem ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Stem Cell Marker ◽  
Hematopoietic Stem

Stem cells contained in the amniotic membrane may be useful for cellular repair of the damaged heart. Previously, we showed that amnion-derived cells (ADCs) express embryonic stem cell surface markers and pluripotent stem cell-specific transcription factor genes. These ADCs also possess the potential for mesoderm (cardiac) lineage differentiation. In the present study we investigated whether untreated naive ADC transplantation into the injured left ventricular (LV) myocardium is beneficial as a cell-based cardiac repair strategy in a rat model. ADCs were isolated from Lewis rat embryonic day 14 amniotic membranes. FACS analysis revealed that freshly isolated ADCs contained stage-specific embryonic antigen-1 (SSEA-1), Oct-4-positive cells, and mesenchymal stromal cells, while hematopoietic stem cell marker positive cells were absent. Reverse transcription-PCR revealed that naive ADCs expressed cardiac and vascular specific genes. We injected freshly isolated ADCs (2 × 106 cells suspended in PBS, ADC group) into acutely infarcted LV myocardium produced by proximal left coronary ligation. PBS was injected in postinfarction controls (PBS group). Cardiac function was assessed at 2 and 6 weeks after injection. ADC treatment attenuated LV dilatation and sustained LV contractile function at 2 and 6 weeks in comparison to PBS controls ( p < 0.05, ANOVA). LV peak systolic pressure and maximum dP/dt of ADC-treated heart were higher and LV end-diastolic pressure and negative dP/dt were lower than in PBS controls ( p < 0.05). Histological assessment revealed that infarcted myocardium of the ADC-treated group had less fibrosis, thicker ventricular walls, and increased capillary density ( p < 0.05). The fate of injected ADCs was confirmed using ADCs derived from EGFP(+) transgenic rats. Immunohistochemistry at 6 weeks revealed that EGFP(+) cells colocalized with von Willebrand factor, α-smooth muscle actin, or cardiac troponin-I. Our results suggest that naive ADCs are a potential cell source for cellular cardiomyoplasty.

Abstract 177: Overexpression of Cardiac Troponin I-Interacting Kinase, a Cardiac-Specific MAPKKK, Promotes Cardiac Dysfunction

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Hao Tang ◽  
Kunhong Xiao ◽  
Lan Mao ◽  
Howard A Rockman ◽  
Douglas A Marchuk
Keyword(s):  
Disease Progression ◽  
Cardiac Dysfunction ◽  
Cardiac Troponin ◽  
Kinase Activity ◽  
Troponin I ◽  
Left Ventricular ◽  
Cardiac Troponin I ◽  
Cardiac Response ◽  
Kinase Assay ◽  
Idiopathic Dilated Cardiomyopathy

Cardiac Troponin I-interacting kinase (TNNI3K) is a cardiac specific kinase whose biological function remains largely unknown. We have recently shown that TNNI3K expression greatly accelerates cardiac dysfunction in mouse models of cardiomyopathy, indicating an important role in modulating disease progression. To further investigate TNNI3K kinase activity in vivo, we have generated transgenic mice expressing both wild-type and kinase-dead versions of the human TNNI3K protein. Importantly, we show that the increased TNNI3K kinase activity induces mouse cardiac hypertrophy, and the kinase activity is required to accelerate disease progression in a left-ventricular pressure overload model of mouse cardiomyopathy. We demonstrate the clinical relevance of these observations by identifying two potential missense mutations near the kinase activation loop of TNNI3K in idiopathic dilated cardiomyopathy (DCM) human patients. Using an in vitro kinase assay and proteomics analysis, we show that TNNI3K is a dual-function kinase with Tyr and Ser/Thr kinase activity. Using antisera to TNNI3K, we show that TNNI3K protein is located at the sarcomere Z disc. These combined data suggest that TNNI3K mediates cell signaling to modulate cardiac response to stress. The essential role of the kinase activity makes TNNI3K a strong potential pharmaceutical target of kinase inhibitors for heart disease.

Abstract P210: Central Blockade Of Tumor Necrosis Factor-Á-Converting Enzyme (tace) Ameliorates Neuroinflammation, Sympathetic Excitation And Cardiac Dysfunction In Heart Failure Rat

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yang Yu ◽  
Baojian Xue ◽  
Hanzeng Li ◽  
Qing Chen ◽  
Mingxuan Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Body Weight ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Cardiac Dysfunction ◽  
Tumor Necrosis ◽  
Left Ventricular ◽  
Male Rats ◽  
Tnf Α ◽  
Necrosis Factor

TACE is a key metalloprotease involved in ectodomain shedding of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-α. We previously reported that TACE-mediated production of TNF-α in the hypothalamic paraventricular nucleus (PVN) contributes to the sympathetic excitation in heart failure (HF). Additionally, the upregulated TGF-α in the PVN transactivates the epidermal growth factor receptor (EGFR) to activate extracellular signal-regulated kinase (ERK) 1/2 in HF. Here we sought to determine whether central inhibition of TACE attenuates neuroinflammation and prevents the progress of HF. Male rats underwent coronary artery ligation to induce HF or sham surgery (Sham). These rats were treated with bilateral PVN microinjection of a TACE siRNA or control siRNA while some rats received a 4-week intracerebroventricular (ICV) infusion of TACE inhibitor TAPI-0 or vehicle. Compared with Sham rats, HF rats treated with control siRNA, had higher (*P<0.05) levels of TNF-α (7.88±1.32* vs 2.77±0.98 pg/mL) and TGF-α (28.27±2.76* vs 11.62±2.48 pg/mL) in cerebrospinal fluid, and increased mRNA expression of TACE (2.53±0.30* vs 1.04±0.12), TNF-α (3.43±0.55* vs 1.03±0.11), TNF-α receptor 1 (2.32±0.27* vs 1.07±0.19), cyclooxygenase-2 (2.96±0.31* vs 1.10±0.19) and TGF-α (2.68±0.41* vs 1.06±0.14) in the PVN, but these levels were markedly reduced (39-54%*) in TACE siRNA-treated HF rats. Compared with control HF rats, HF rats treated with TACE siRNA had reduced expression of phosphorylated (p-) NF-κB p65 (1.27±0.14 vs 0.84±0.07*), p-EGFR (0.52±0.05 vs 0.37±0.04*) and p-ERK1/2 (1.06±0.10 vs 0.62±0.09*) in the PVN. Moreover, the elevated plasma norepinephrine levels, lung/body weight, heart/body weight and left ventricular (LV) end-diastolic pressure along with decreased LV dP/dt max in HF rats-treated with control siRNA were significantly attenuated in HF rats treated with TACE siRNA. Treatments with TACE siRNA in the PVN also improved the indicators of cardiac hypertrophy and fibrosis of HF. ICV infusion of TAPI-0 had the similar effects with PVN TACE siRNA on these variables in HF. These data indicate that central interventions suppressing TACE activity ameliorate neuroinflammation, sympathetic activation and cardiac dysfunction in HF.

DNA enzyme targeting TNF-α mRNA improves hemodynamic performance in rats with postinfarction heart failure

2001 ◽  
Vol 281 (5) ◽  
pp. H2211-H2217 ◽  
Author(s):  
Per Ole Iversen ◽  
Gunnar Nicolaysen ◽  
Mouldy Sioud
Keyword(s):  
Heart Failure ◽  
Therapeutic Potential ◽  
Diastolic Pressure ◽  
Substantial Reduction ◽  
Left Ventricular ◽  
Lung Weight ◽  
Cleavage Activity ◽  
Arterial Blood ◽  
Modified Dna ◽  
Tnf Α

Tumor necrosis factor-α (TNF-α) probably affects the pathogenesis of heart failure. Here we have investigated the therapeutic potential of a nuclease-resistant DNA enzyme that specifically cleaves TNF-α mRNA. A phosphorothioate-modified DNA enzyme was designed to retain similar cleavage activity as its unmodified version, and that inhibited the expression of TNF-α in vitro. To test its efficacy in vivo, postinfarction congestive heart failure was induced in anesthetized rats by ligation of the left coronary artery. A 4-wk treatment with the DNA enzyme induced a substantial reduction in left ventricular end-diastolic pressure and lung weight concomitant with an increase in arterial blood pressure and myocardial blood flow compared with controls. The concentration of TNF-α in coronary sinus blood was markedly lowered on treatment, and myocardial TNF-α mRNA was substantially reduced. Recovery studies showed that the DNA enzyme cleavage activity was present within the myocardium throughout the observation period and had no apparent toxic effects. Our findings indicate that DNA enzyme-based therapy may hold promise in the treatment of this debilitating disease.

The Effect of Gypenosides on Cardiac Function and Expression of Cytoskeletal Genes of Myocardium in Diabetic Cardiomyopathy Rats

2009 ◽  
Vol 37 (06) ◽  
pp. 1059-1068 ◽  
Author(s):  
Min Ge ◽  
Shanfeng Ma ◽  
Liang Tao ◽  
Sudong Guan
Keyword(s):  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Diastolic Pressure ◽  
Pure Water ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Sprague Dawley ◽  
Gene Expressions ◽  
Ventricular Systolic Pressure

The relationship between changes of cardiac function and the gene expressions of two major myocardial skeleton proteins, titin and nebulin, and the effect of gypenosides on these gene expressions in diabetic cardiomyopathy rat were explored in the present study. Forty Sprague-Dawley rats were randomly divided into three groups: control group, diabetic cardiomyopathy group and gypenosides-treated diabetic cardiomyopathy group. The diabetic cardiomyopathy was induced in rats by injecting streptozotocin (STZ, 55 mg/kg) intraperitoneally. Seven weeks after the rats suffered from diabetes, the rats were treated with gypenosides 100 mg/kg per day orally for six weeks in gypenosides-treated group. In the meanwhile, the pure water was given to diabetic cardiomyopathy and the control groups. Subsequently, the cardiac functions, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), ± dP/dtmax and t–dP/dmaxt, as well as the mRNA content and proteins of titin and nebulin in myocardium were determined. The results indicated that (1) the diabetic cardiomyopathy rats had decreased LVSP and ± dP/dtmax, increased LVEDP, and prolonged t–dP/dtmax than normal rats; (2) LVSP and ± dP/dtmax in diabetic cardiomyopathy rats treated with gypenosides were significantly higher and LVEDP and t–dP/dtmax were significantly lower than those without giving gypenosides; (3) the mRNA contents and proteins of titin and nebulin in diabetic cardiomyopathy rats were remarkably lower than those in the control rats and gypenosides had no effect on mRNA and protein expression levels of titin and nebulin in diabetic cardiomyopathy rats. We conclude that (1) the cardiac function as well as the mRNA expressions of titin and nebulin decreased in diabetic cardiomyopathy rats; (2) gypenosides secure cardiac muscles and their function from diabetic impairment and these beneficial effects of gypenosides are not by changing the expressions of titin and nebulin.

Trastuzumab-Induced Cardiotoxicity: Clinical and Prognostic Implications of Troponin I Evaluation

2010 ◽  
Vol 28 (25) ◽  
pp. 3910-3916 ◽  
Author(s):  
Daniela Cardinale ◽  
Alessandro Colombo ◽  
Rosalba Torrisi ◽  
Maria T. Sandri ◽  
Maurizio Civelli ◽  
...  
Keyword(s):  
At Risk ◽  
Cardiac Dysfunction ◽  
Troponin I ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Trastuzumab Therapy ◽  
Before And After ◽  
Patients At Risk ◽  
Prognostic Implications

Purpose Treatment of breast cancer with trastuzumab is complicated by cardiotoxicity in up to 34% of the patients. In most patients, trastuzumab-induced cardiotoxicity (TIC) is reversible: left ventricular ejection fraction (LVEF) improves after trastuzumab withdrawal and with, or sometimes without, initiation of heart failure (HF) therapy. The reversibility of TIC, however, is not foreseeable, and identification of patients at risk and of those who will not recover from cardiac dysfunction is crucial. The usefulness of troponin I (TNI) in the identification of patients at risk for TIC and in the prediction of LVEF recovery has never been investigated. Patients and Methods In total, 251 women were enrolled. TNI was measured before and after each trastuzumab cycle. LVEF was evaluated at baseline, every 3 months during trastuzumab therapy, and every 6 months afterward. In case of TIC, trastuzumab was discontinued, and HF treatment with enalapril and carvedilol was initiated. TIC was defined as LVEF decrease of > 10 units and below 50%. Recovery from TIC was defined as LVEF increase above 50%. Results TIC occurred in 42 patients (17%) and was more frequent in patients with TNI elevation (TNI+; 62% v 5%; P < .001). Twenty-five patients (60%) recovered from TIC. LVEF recovery occurred less frequently in TNI+ patients (35% v 100%; P < .001). At multivariate analysis, TNI+ was the only independent predictor of TIC (hazard ratio [HR], 22.9; 95% CI, 11.6 to 45.5; P < .001) and of lack of LVEF recovery (HR, 2.88; 95% CI,1.78 to 4.65; P < .001). Conclusion TNI+ identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.

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