Cardiac Function Normalizes 1 Year After Bariatric Surgery in Half of the Obesity Patients with Subclinical Cardiac Dysfunction

Background: The N-Terminal of pro-B-type natriuretic peptide (NT-proBNP) is a potent biomarker for heart failure (HF), reflecting left ventricular dilation and stress. The association among obesity, HF, and NT-proBNP is complex, with paradoxically lower levels of NT-proBNP in obese individuals, despite their elevated HF risk. Furthermore, a few studies have reported decreased HF risk, but also increases in NT-proBNP, after weight loss via bariatric surgery. However, studies have not simultaneously evaluated changes in NT-proBNP and cardiac function after bariatric surgery. Hypothesis: There will be discordance between improvements in cardiac filling pressures (as reflected by E/e’) and increases in NT-proBNP with weight loss following bariatric surgery. Methods: We conducted a single-center analysis of participants in the BARI-Heart Study who underwent bariatric surgery and attended study visits 3-6 months and 2 weeks before surgery, and 6 and 12 months after surgery. We examined pre- and post-surgery changes in NT-proBNP and in echocardiographic measures of cardiac function. We also assessed the correlation between NT-pro-BNP and E/e’, at 2 weeks pre- and 6 months post-surgery. Results: Among 71 BARI-Heart participants (mean age 45 years, 74% female, 87% white, mean BMI 47.0 kg/m 2 ), there were no significant pre-surgery changes in BMI, NT-proBNP, or E/e’. By 6-12 months, there were marked reductions in BMI and significant increases in NT-proBNP, but decreases in E/e’ ( Figure ). Changes from surgery to the 6 month visit in NT-proBNP and E/e’ were associated (r=0.295; p=0.02). There was a tendency towards stronger correlations between NT-proBNP and E/e’ post- (r= 0.436; p<0.001) versus pre-surgery (r = 0.209; p=0.09). Conclusions: Weight loss is associated with increases in NT-proBNP despite reduced LV filling pressures, suggesting a non-cardiac etiology underlying increases in NT-proBNP after weight loss. The interpretation of NT-proBNP for cardiac dysfunction may change with decreasing adiposity.

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Exercise cardiac MRI unmasks cardiac dysfunction in childhood and adolescent cancer survivors with reduced cardiopulmonary fitness

European Heart Journal ◽

10.1093/ehjci/ehaa946.3275 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Foulkes ◽

B Costello ◽

E.J Howden ◽

K Janssens ◽

H Dillon ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Cancer Survivors ◽

Pediatric Cancer ◽

Cardiac Dysfunction ◽

Cardiopulmonary Fitness ◽

Cardiac Reserve ◽

Pediatric Cancer Survivors ◽

Increased Risk

Abstract Background Young cancer survivors are at increased risk of impaired cardiopulmonary fitness (VO2peak) and heart failure. Assessment of exercise cardiac reserve may reveal sub-clinical abnormalities that better explain impairments in fitness and long term heart failure risk. Purpose To investigate the presence of impaired VO2peak in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac reserve Methods Twenty pediatric cancer survivors (aged 8–24 years) treated with anthracycline chemotherapy underwent cardiopulmonary exercise testing to quantify VO2peak, with a value <85% of predicted defined as impaired VO2peak. Resting cardiac function was assessed using 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate (HR), stroke volume index (SVi) and cardiac index (CI) using exercise cardiac magnetic resonance imaging. Results 12 of 20 survivors (60%) had impaired VO2peak (97±14% vs. 70±16% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired VO2peak. However, those with reduced VO2peak had diminished cardiac reserve, with a lesser increase in CI (Fig. 1A) and SVi (Fig. 1B) during exercise (Interaction P=0.001 for both), whilst the HR response was similar (Fig. 1C; P=0.71). Conclusions Resting measures of cardiac function are insensitive to significant cardiac dysfunction amongst pediatric cancer survivors with reduced VO2peak. Measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Heart Foundation

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Exposure to Δ9-tetrahydrocannabinol during rat pregnancy leads to impaired cardiac dysfunction in postnatal life

Pediatric Research ◽

10.1038/s41390-021-01511-9 ◽

2021 ◽

Author(s):

Kendrick Lee ◽

Steven R. Laviolette ◽

Daniel B. Hardy

Keyword(s):

Body Weight ◽

Cardiac Function ◽

Cardiac Dysfunction ◽

Cardiac Remodelling ◽

Long Term Effects ◽

Catch Up ◽

First Time ◽

Impaired Cardiac Function ◽

In Pregnancy

Abstract Background Cannabis use in pregnancy leads to fetal growth restriction (FGR), but the long-term effects on cardiac function in the offspring are unknown, despite the fact that fetal growth deficits are associated with an increased risk of developing postnatal cardiovascular disease. We hypothesize that maternal exposure to Δ9-tetrahydrocannabinol (Δ9-THC) during pregnancy will impair fetal development, leading to cardiac dysfunction in the offspring. Methods Pregnant Wistar rats were randomly selected and administered 3 mg/kg of Δ9-THC or saline as a vehicle daily via intraperitoneal injection from gestational days 6 to 22, followed by echocardiogram analysis of cardiac function on offspring at postnatal days 1 and 21. Heart tissue was harvested from the offspring at 3 weeks for molecular analysis of cardiac remodelling. Results Exposure to Δ9-THC during pregnancy led to FGR with a significant decrease in heart-to-body weight ratios at birth. By 3 weeks, pups exhibited catch-up growth associated with significantly greater left ventricle anterior wall thickness with a decrease in cardiac output. Moreover, these Δ9-THC-exposed offsprings exhibited increased expression of collagen I and III, decreased matrix metallopeptidase-2 expression, and increased inactivation of glycogen synthase kinase-3β, all associated with cardiac remodelling. Conclusions Collectively, these data suggest that Δ9-THC-exposed FGR offspring undergo postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function early in life. Impact To date, the long-term effects of perinatal Δ9-THC (the main psychoactive component) exposure on the cardiac function in the offspring remain unknown. We demonstrated, for the first time, that exposure to Δ9-THC alone during rat pregnancy results in significantly smaller hearts relative to body weight. These Δ9-THC-exposed offsprings exhibited postnatal catch-up growth concomitant with cardiac remodelling and impaired cardiac function. Given the increased popularity of cannabis use in pregnancy along with rising Δ9-THC concentrations, this study, for the first time, identifies the risk of perinatal Δ9-THC exposure on early postnatal cardiovascular health.

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Assessment of Cardiac Dysfunction in the Intrauterine Growth-restricted Fetuses from Pre-eclamptic Mothers

Donald School Journal of Ultrasound in Obstetrics & Gynecology ◽

10.5005/jp-journals-10009-1346 ◽

2014 ◽

Vol 8 (2) ◽

pp. 123-127

Author(s):

Florin Stamatian ◽

Gabriela Caracostea

Keyword(s):

Cardiac Function ◽

Cardiac Dysfunction ◽

Sequential Analysis ◽

Tissue Doppler ◽

Severe Form ◽

Doppler Imaging ◽

Diastolic Filling ◽

Intrauterine Growth ◽

Performance Indexes ◽

Left And Right

ABSTRACT Background Although it is known that cardiac parameters have abnormal values in severely affected fetuses with intrauterine growth restriction (IUGR), recent research suggested that subclinical cardiac dysfunction may be present from the early stages of fetal deterioration. The identification and monitoring of cardiac dysfunction may be relevant for the management of these cases. Materials and methods In this prospective observational study, we evaluated 17 IUGR fetuses from nulliparous pregnant women diagnosed with pre-eclampsia. Cardiac structural assessment was performed using segmental sequential analysis. Cardiac function was assessed by conventional echocardiography and Tissue Doppler Imaging (TDI). Results Gestational age at admittance ranged between 24 and 30 weeks. A severe form of pre-eclampsia was diagnosed in 2 of 17 cases. Conventional cardiac examination showed low left and right ventricular diastolic filling with low E and A velocities, and increased myocardial performance indexes for both ventricles. Using TDI we observed decreased myocardial velocities and impaired contractility (demonstrated by low left and right diastolic velocities, as well as increased E’/A’ ratios). Conclusion Our study confirms the presence of early cardiac dysfunction in IUGR fetuses. Further studies are warranted to confirm the utility of TDI in obstetric ultrasound routine examination for monitoring fetal cardiac function in high-risk pregnancies. How to cite this article Caracostea G, Stamatian F. Assessment of Cardiac Dysfunction in the Intrauterine Growthrestricted Fetuses from Pre-eclamptic Mothers. Donald School J Ultrasound Obstet Gynecol 2014;8(2):123-127.

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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 12153: Impact of a Hybrid Nurse-Led Intervention for the Prevention of Progressive Cardiac Dysfunction in High Risk Individuals: Results From a Pragmatic, Randomized Trial (the NIL-CHF Study)

Circulation ◽

10.1161/circ.130.suppl_2.12153 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Simon Stewart ◽

Melinda Carrington ◽

Yih Kai Chan ◽

Garry Jennings ◽

Chiew Wong ◽

...

Keyword(s):

High Risk ◽

Cardiac Function ◽

Diastolic Dysfunction ◽

Cardiac Dysfunction ◽

Systolic Dysfunction ◽

Cardiac Abnormality ◽

Coronary Syndrome ◽

History Of ◽

Hybrid Program

Background: The natural history of chronic heart failure (CHF) is characterized by initial cardiac insult and/or stressors over time that leaves affected individuals at high risk for progressive cardiac dysfunction and eventual development of the syndrome. Methods: Of a total of 624 subjects at high risk of developing CHF randomized into the NIL-CHF Study comparing a hybrid program of home and clinic-based follow-up (NIL-CHF group) to Standard Care, 454 (73%) underwent serial echocardiography at 1 month post index cardiac hospitalization and at 3 years. At both time points (nil signs/symptoms of CHF at baseline), these were blindly classified as follows: 1) no cardiac abnormality, 2) systolic dysfunction/HFrEF - LVEF ≤ 45% ), 3) diastolic dysfunction/HFpEF as defined by any moderate diastolic dysfunction (with pseudonormalization pattern) or E/E prime ratio ≥ 15, 4) combination of 2 & 3 and 5) other cardiac abnormality (including LVH). Pre-specified criteria were used to determine - i) no change, ii) improvement or iii) deterioration in cardiac function from baseline to 3 years. Results: Mean age was 66±11 years, 71% were male, 70% were hospitalized with an acute coronary syndrome and 62% and 26%, respectively, were being treated for hypertension and diabetes. At baseline 25.2% vs. 28.4% (p=ns), 15.1% vs. 9.1% (p<0.05), 35.1% vs. 32.4% (p=ns) and 34.3% vs. 39.6% had normal cardiac function, HFrEF, HFpEF (13% both HFrEF and HFpEF overall) and LVH (the predominant “other” cardiac abnormality), respectively. At 3 years the proportion of subjects with reversal of pre-existing HFrEF or HFpEF was lower in the NIL-CHF group (23% vs. 16%; p=0.063). Moreover, significantly more NIL-CHF subjects demonstrated any form of cardiac recovery/reversal on echocardiography (39% vs. 25%, p=0.011, 95% CI 1.35, 95% CI 1.04, 1.76). They also demonstrated significantly greater regression to normal LV structure (36% vs. 25%; p=0.047) among those with LVH at baseline. Conclusions: These pre-specified analyses (secondary endpoint) of the recently completed NIL-CHF Study suggests a cardio-protective effect conferred by a long-term, nurse-led, home and clinic-based intervention targeting hospitalized individuals at high risk for developing CHF.

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Assessment of foetal cardiac function by myocardial tissue doppler in foetal growth restriction

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20170582 ◽

2017 ◽

Vol 6 (3) ◽

pp. 1045

Author(s):

Barnali Basu ◽

Ranjan Shetty ◽

Krishnendu Gupta

Keyword(s):

Cardiac Function ◽

Cardiac Dysfunction ◽

Tertiary Care ◽

Normal Growth ◽

Tissue Doppler ◽

Myocardial Tissue ◽

Third Trimester ◽

Foetal Growth Restriction ◽

Adverse Neonatal Outcomes ◽

A New Technique

Background: One of the consequences of IUGR is the development of cardiac diastolic dysfunction in fetuses. Tissue doppler in echocardiography is a new technique to detect myocardial tissue function and can act as a useful tool in the identification of this complication. Hence we decided to undertake this study to assess the utility of myocardial tissue doppler in detecting foetal cardiac dysfunction in IUGR. It was a prospective case control study in a tertiary care teaching hospital.Methods: Foetal cardiac function in the third trimester of pregnancy was evaluated with the help of myocardial tissue doppler and compared between IUGR and normal growth babies and correlated with vessel doppler findings and neonatal outcomes.Results: There were sixty two IUGR and fifty eight normal growth babies in the study. In babies with IUGR, particularly the ones with severe IUGR, abnormal vessel doppler and adverse neonatal outcomes, right ventricular MPI was found to be significantly lower. However, the variable had a poor sensitivity (40%) in detecting fetuses at risk for poor neonatal outcomes.Conclusions: Myocardial tissue doppler shows right sided cardiac dysfunction in IUGR babies in comparison to normal growth babies It is however not a sensitive indicator of adverse perinatal outcome in IUGR babies.

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Aerobic Exercise Attenuates Pressure Overload-Induced Cardiac Dysfunction through Promoting Skeletal Muscle Microcirculation and Increasing Muscle Mass

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8279369 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Ling-Yan Yuan ◽

Pei-Zhao Du ◽

Min-Min Wei ◽

Qi Zhang ◽

Le Lu ◽

...

Keyword(s):

Skeletal Muscle ◽

Cardiac Function ◽

Aerobic Exercise ◽

Muscle Mass ◽

Cardiac Dysfunction ◽

Pressure Overload ◽

Transverse Aortic Constriction ◽

Aortic Constriction ◽

Protein Levels ◽

Skeletal Muscle Microcirculation

Background. Aerobic exercise has been proven to have a positive effect on cardiac function after hypertension; however, the mechanism is not entirely clarified. Skeletal muscle mass and microcirculation are closely associated with blood pressure and cardiac function. Objective. This study was designed to investigate the effects of aerobic exercise on the skeletal muscle capillary and muscle mass, to explore the possible mechanisms involved in exercise-induced mitigation of cardiac dysfunction in pressure overload mice. Methods. In this study, 60 BALB/C mice aged 8 weeks were randomly divided into 3 groups: control (CON), TAC, and TAC plus exercise (TAE) group and utilized transverse aortic constriction (TAC) to establish hypertensive model; meanwhile, treadmill training is used for aerobic exercise. After 5 days of recovery, mice in the TAE group were subjected to 10-week aerobic exercise. Carotid pressure and cardiac function were examined before mice were executed by Millar catheter and ultrasound, respectively. Muscle mass of gastrocnemius was weighed; cross-sectional area and the number of capillaries of gastrocnemius were detected by HE and immunohistochemistry, respectively. The mRNA and protein levels of VEGF in skeletal muscle were determined by RT-PCR and western blot, respectively. Results. We found that ① 10-week aerobic exercise counteracted hypertension and attenuated cardiac dysfunction in TAC-induced hypertensive mice; ② TAC decreased muscle mass of gastrocnemius and resulted in muscle atrophy, while 10-week aerobic exercise could reserve transverse aortic constriction-induced the decline of muscle mass and muscle atrophy; and ③ TAC reduced the number of capillaries and the protein level of VEGF in gastrocnemius, whereas 10-week aerobic exercise augmented the number of capillaries, the mRNA and protein levels of VEGF in mice were subjected to TAC surgery. Conclusions. This study indicates that 10-week aerobic exercise might fulfill its blood pressure-lowering effect via improving skeletal muscle microcirculation and increasing muscle mass.

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Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production

Frontiers in Pharmacology ◽

10.3389/fphar.2020.614024 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xin-Tong Wang ◽

Zhen Peng ◽

Ying-Ying An ◽

Ting Shang ◽

Guangxu Xiao ◽

...

Keyword(s):

Cardiac Function ◽

Cardiac Dysfunction ◽

Cardiac Tissue ◽

Myocardial Dysfunction ◽

Cecal Ligation ◽

Hydroxysafflor Yellow A ◽

Sepsis Management ◽

Xuebijing Injection

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.

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A Transcriptional Switch Governing Fibroblast Plasticity Underlies Reversibility of Chronic Heart Disease

10.1101/2020.07.21.214874 ◽

2020 ◽

Author(s):

Michael Alexanian ◽

Pawel F. Przytycki ◽

Rudi Micheletti ◽

Arun Padmanabhan ◽

Lin Ye ◽

...

Keyword(s):

Heart Disease ◽

Cardiac Function ◽

Single Cell ◽

Cardiac Dysfunction ◽

Cardiac Fibroblasts ◽

Regulatory Elements ◽

Heart Tissue ◽

Chromatin Accessibility ◽

Fibroblast Activation ◽

Transcriptional Switch

AbstractIn diseased organs, stress-activated signaling cascades alter chromatin, triggering broad shifts in transcription and cell state that exacerbate pathology. Fibroblast activation is a common stress response that worsens lung, liver, kidney and heart disease, yet its mechanistic basis remains poorly understood1,2. Pharmacologic inhibition of the BET family of transcriptional coactivators alleviates cardiac dysfunction and associated fibrosis, providing a tool to mechanistically interrogate maladaptive fibroblast states and modulate their plasticity as a potential therapeutic approach3–8. Here, we leverage dynamic single cell transcriptomic and epigenomic interrogation of heart tissue with and without BET inhibition to reveal a reversible transcriptional switch underlying stress-induced fibroblast activation. Transcriptomes of resident cardiac fibroblasts demonstrated robust and rapid toggling between the quiescent fibroblast and activated myofibroblast state in a manner that directly correlated with BET inhibitor exposure and cardiac function. Correlation of single cell chromatin accessibility with cardiac function revealed a novel set of reversibly accessible DNA elements that correlated with disease severity. Among the most dynamic elements was an enhancer regulating the transcription factor MEOX1, which was specifically expressed in activated myofibroblasts, occupied putative regulatory elements of a broad fibrotic gene program, and was required for TGFβ-induced myofibroblast activation. CRISPR interference of the most dynamic cis-element within the enhancer, marked by nascent transcription, prevented TGFβ-induced activation of Meox1. These findings identify MEOX1 as a central regulator of stress-induced myofibroblast activation associated with cardiac dysfunction. The plasticity and specificity of the BET-dependent regulation of MEOX1 in endogenous tissue fibroblasts provides new trans- and cis- targets for treating fibrotic disease.

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