Left Ventricular Cardiac Dysfunction in the Diaphragmatic Hernia Fetus: Fetal Phenotypic Improvement Is Seen with Tracheal Occlusion

Congenital diaphragmatic hernia is one of the rare malformations (0.8-5 / 10000). Although there are many treatment options in the postnatal period, as the severity of the malformation increases, the response to treatment decreases. Lung development is restricted by the compression of intraabdominal organs passing through the diaphragmatic defect. The severity of pulmonary hypertension due to hypoplasia in the lung tissue is closely related to postnatal morbidity and mortality. In addition to the lung tissue, left ventricular hypoplasia may also occur due to pressure on the heart. For all these reasons, treatment options have begun to be investigated even in the prenatal period, before tissue hypoplasia develops. In the last 20 years, there have been serious developments in ultrasound and magnetic resonance devices in parallel with the developments in technology. Accordingly, lung development of fetuses with diaphragmatic hernia during prenatal period has been better followed. Fetal endoscopic tracheal occlusion is the only method that can give treatment options to patients who are found to have severely decreased lung tissue in the prenatal period, in order to increase postpartum life expectancy. With this procedure, it is aimed to collect the fluids released from the lung with a balloon placed in the trachea in the prenatal period. Because of these accumulated fluids, the lung volume expands, tissue hypoplasia decreases, and the degree of pulmonary hypertension decreases. Although the fetal tracheal occlusion procedure has improved neonatal outcomes, there is a possibility of complications depending on the way the procedure is applied. Various complications such as premature rupture of membranes and preterm labor can be seen depending on the procedure. For this reason, it is necessary to choose the candidates for the tracheal occlusion procedure well and to calculate the profit-loss ratio well. In this study, current publications of fetal endoscopic tracheal occlusion procedure were reviewed. It was investigated on which patients the procedure could be applied and what the benefits and harms might be if it was applied.

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Fetal Endoscopic Tracheal Occlusion (FETO) Trial for Congenital Diaphragmatic Hernia (CDH)

Case Medical Research ◽

10.31525/ct1-nct04052828 ◽

2019 ◽

Author(s):

Keyword(s):

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Tracheal Occlusion

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Subtle cardiac dysfunction in lymphoma patients receiving low to moderate dose chemotherapy

Scientific Reports ◽

10.1038/s41598-021-86652-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hsien-Yuan Chang ◽

Chun-Hui Lee ◽

Po-Lan Su ◽

Sin-Syue Li ◽

Ming-Yueh Chen ◽

...

Keyword(s):

Cancer Therapy ◽

Exercise Capacity ◽

Cardiac Dysfunction ◽

Primary Outcome ◽

Early Stage ◽

Systolic Dysfunction ◽

Anticancer Therapy ◽

Cardiopulmonary Exercise Test ◽

Left Ventricular ◽

Relative Reduction

AbstractLeft ventricular (LV) global peak systolic longitudinal strain (GLS) is a sensitive measurement for detecting subtle LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving cancer therapy remains unknown. We prospectively enrolled 74 lymphoma patients (57.9 ± 17.0 years old, 57% male). We performed echocardiographic studies after the 3rd and 6th cycles and 1 year after chemotherapy and a cardiopulmonary exercise test upon completion of 3 cycles of anticancer therapy. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a ≥ 15% relative reduction in GLS value from baseline. The primary outcome was a composite of all-cause mortality and heart failure events. Thirty-six patients (49%) had CTRCD (LV GLS: baseline vs. after 3rd cycle of therapy: 20.1 ± 2.6 vs. 17.5 ± 2.3%, p < 0.001). CTRCD was detected after the 3rd cycle of anticancer therapy. CTRCD patients had impaired exercise capacity (minute oxygen consumption/kg, CTRCD vs. CTRCD (-): 13.9 ± 3.1 vs. 17.0 ± 3.9 ml/kg/min, p = 0.02). More primary outcome events occurred in the CTRCD group (hazard ratio 3.21; 95% confidence interval 1.04–9.97; p = 0.03). LV GLS could detect subtle but clinically significant cardiac dysfunction in lymphoma patients in the early stage of anticancer therapy. CTRCD may be associated with not only a reduced exercise capacity but also a worse prognosis.

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Very early detection of low dose anti-cancer therapy-related cardiotoxicity in lymphoma patients

European Heart Journal ◽

10.1093/ehjci/ehaa946.3257 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y.W Liu ◽

H.Y Chang ◽

C.H Lee ◽

W.C Tsai ◽

P.Y Liu ◽

...

Keyword(s):

Heart Failure ◽

Cancer Therapy ◽

Cardiac Dysfunction ◽

Systolic Dysfunction ◽

Multivariable Analysis ◽

Cardiopulmonary Exercise Test ◽

Left Ventricular ◽

Funding Source ◽

Anti Cancer ◽

All Cause Mortality

Abstract Background and purpose Left ventricular (LV) global peak systolic longitudinal strain (GLS) by speckle-tracking echocardiography is a sensitive modality for the detection of subclinical LV systolic dysfunction and a powerful prognostic predictor. However, the clinical implication of LV GLS in lymphoma patients receiving anti-cancer therapy remains unknown. Methods We prospectively enrolled 74 patients (57.9±17.0 years old, 57% male) with lymphoma who underwent echocardiography prior to chemotherapy, post 3rd and 6th cycle and 1 year after chemotherapy. Cancer therapy-related cardiac dysfunction (CTRCD) is defined as the reduction of absolute GLS value from baseline of ≥15%. All the eligible patients underwent a cardiopulmonary exercise test (CPET) upon completion of 3 cycles of anti-cancer therapy. The primary outcome was defined as a composite of all-cause mortality and heart failure events. Results Among 36 (49%) patients with CTRCD, LV GLS was significantly decreased after the 3rd cycle of chemotherapy (20.1±2.6% vs. 17.5±2.3%, p<0.001). In the multivariable analysis, male sex and anemia (hemoglobin <11 g/dL) were found to be independent risk factors of CTRCD. Objectively, patients with CTRCD had lower minute oxygen consumption/kg (VO2/kg) and lower VO2/kg value at anaerobic threshold in the CPET. The incidence of the primary composite outcome was higher in the CTRCD group than in the non-CTRCD group (hazard ratio 3.21; 95% CI, 1.04–9.97; p=0.03). Conclusion LV GLS is capable of detecting early cardiac dysfunction in lymphoma patients receiving anti-cancer therapy. Patients with CTRCD not only had a reduced exercise capacity but also a higher risk of all-cause mortality and heart failure events. Change of LVEF and GLS after cancer Tx Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Ministry of Science and Technology (MOST), Taiwan

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Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01142.2008 ◽

2009 ◽

Vol 297 (1) ◽

pp. H153-H162 ◽

Cited By ~ 114

Author(s):

Sabrina Serpillon ◽

Beverly C. Floyd ◽

Rakhee S. Gupte ◽

Shimran George ◽

Mark Kozicky ◽

...

Keyword(s):

Cardiac Dysfunction ◽

Rat Heart ◽

Mitochondrial Respiratory Chain ◽

Posterior Wall ◽

Left Ventricular ◽

Posterior Wall Thickness ◽

Patients With Diabetes ◽

Protein Kinase C Inhibitor ◽

Glucose 6 Phosphate Dehydrogenase

Increased oxidative stress is a known cause of cardiac dysfunction in animals and patients with diabetes, but the sources of reactive oxygen species [e.g., superoxide anion (O2−)] and the mechanisms underlying O2− production in diabetic hearts are not clearly understood. Our aim was to determine whether NADPH oxidase (Nox) is a source of O2− and whether glucose-6-phosphate dehydrogenase (G6PD)-derived NADPH plays a role in augmenting O2− generation in diabetes. We assessed cardiac function, Nox and G6PD activities, NADPH levels, and the activities of antioxidant enzymes in heart homogenates from young (9–11 wk old) Zucker lean and obese (fa/fa) rats. We found that myocardial G6PD activity was significantly higher in fa/fa than in lean rats, whereas superoxide dismutase and glutathione peroxidase activities were decreased ( P < 0.05). O2− levels were elevated (70–90%; P < 0.05) in the diabetic heart, and this elevation was blocked by the Nox inhibitor gp-91ds-tat (50 μM) or by the mitochondrial respiratory chain inhibitors antimycin (10 μM) and rotenone (50 μM). Inhibition of G6PD by 6-aminonicotinamide (5 mM) and dihydroepiandrosterone (100 μM) also reduced ( P < 0.05) O2− production. Notably, the activities of Nox and G6PD in the fa/fa rat heart were inhibited by chelerythrine, a protein kinase C inhibitor. Although we detected no changes in stroke volume, cardiac output, or ejection fraction, left ventricular diameter was slightly increased during diastole and systole, and left ventricular posterior wall thickness was decreased during systole ( P < 0.05) in Zucker fa/fa rats. Our findings suggest that in a model of severe hyperlipidema and hyperglycemia Nox-derived O2− generation in the myocardium is fueled by elevated levels of G6PD-derived NADPH. Similar mechanisms were found to activate O2− production and induce endothelial dysfunction in aorta. Thus G6PD may be a useful therapeutic target for treating the cardiovascular disease associated with type 2 diabetes, if second-generation drugs specifically reducing the activity of G6PD to near normal levels are developed.

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Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.09.1611 ◽

2007 ◽

Vol 25 (25) ◽

pp. 3859-3865 ◽

Cited By ~ 378

Author(s):

Thomas M. Suter ◽

Marion Procter ◽

Dirk J. van Veldhuisen ◽

Michael Muscholl ◽

Jonas Bergh ◽

...

Keyword(s):

Breast Cancer ◽

Adjuvant Chemotherapy ◽

Adverse Effects ◽

Cancer Patients ◽

Cardiac Dysfunction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Breast Cancer Patients ◽

Ventricular Ejection Fraction ◽

Neo Adjuvant Chemotherapy

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

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O-023 Candidate Biomarkers Of Pulmonary Hypertension And Cardiac Dysfunction In Congenital Diaphragmatic Hernia: Abstract O-023 Table 1

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-307384.92 ◽

2014 ◽

Vol 99 (Suppl 2) ◽

pp. A30.2-A31 ◽

Cited By ~ 1

Author(s):

N Patel ◽

F Moenkemeyer

Keyword(s):

Pulmonary Hypertension ◽

Congenital Diaphragmatic Hernia ◽

Diaphragmatic Hernia ◽

Cardiac Dysfunction

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Abstract 1213: Cardiac Overexpression of Epac1 in Transgenic Mice Protects Heart from Lipopolysaccharide-induced Cardiac Dysfunction and Inhibits JAK-STAT Pathway

Circulation ◽

10.1161/circ.116.suppl_16.ii_246-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Satoshi Okumura ◽

Yunzhe Bai ◽

Meihua Jin ◽

Sayaka Suzuki ◽

Akiko Kuwae ◽

...

Keyword(s):

Heart Failure ◽

Cyclic Amp ◽

Transgenic Mice ◽

Cardiac Function ◽

Proinflammatory Cytokines ◽

Cardiac Dysfunction ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Stat Pathway

The sympathetic nervous system and proinflammatory cytokines are believed to play independent roles in the pathophysiology of heart failure. However, the recent identification of Epac (exchange protein activated by cyclic AMP), a new cyclic AMP-binding protein that directly activates Rap1, have implicated that there may be a potential cross talk between the sympathetic and cytokine signals. In order to examine the role of Epac in cytokine signal to regulate cardiac function, we have generated transgenic mice expressing the human Epac1 gene under the control of alpha-cardiac myosin heavy chain promoter (Epac1-TG), and examined their response in lipopolysaccharide (LPS)-induced cardiac dysfunction, a well established model for sepsis-induced cardiac dysfunction. Sepsis-induced cardiac dysfunction results from the production of proinflammatory cytokines. At baseline, left ventricular ejection fraction (LVEF) was similar (TG vs. NTG, 67±1.7 vs. 69±2.1%, n =7–9). The degree of cardiac hypertrophy (LV(mg)/tibia(mm)) was also similar at 3 months old (TG vs. NTG 4.0±0.1 vs. 4.2±0.1, n =5–6), but it became slightly but significantly greater in Epac1-TG at 5 month old (TG vs. NTG 4.9±0.1 vs. 4.4±0.1, p< 0.05, n =5–7). LPS (5mg/kg) elicited a significant and robust reduction of LVEF in both Epac1-TG and NTG, but the magnitude of this decrease was much less in Epac1-TG at 6 hr after injection (TG vs. NTG 48±2.4 vs. 57±1.8%, p< 0.01, n =6–9). At 24 hr after injection, cardiac function was restored to the baseline in both Epac1-TG and NTG. We also examined the activation of JAK-STAT pathway at 24 hr after injection. The tyrosine phosphorylation of STAT1 (Tyr701) and STAT3 (Tyr705) in LV, which is an indicator of STAT activation, was reduced to a greater degree in Epac1-TG by 31±8.8% ( p< 0.05, n =4) and 29±5.9% ( p< 0.05, n =7), respectively, relative to that in NTG. Taken together, Epac1 protects the heart from the cytokine-induced cardiac dysfunction, at least in part, through the inhibition of the JAK-STAT pathway, suggesting the beneficial role played by sympathetic signal to antagonize proinflammatory cytokine signal in heart failure.

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

Circulation Research ◽

10.1161/res.111.suppl_1.a177 ◽

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.

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