Tissue Inhibitor of Metalloproteinase-1 Is Increased in Chagasic Cardiomyopathy

Chagas disease (CD) mainly conveys stroke risk through structural cardiac disease. However, stroke and cognitive impairment are seen in CD independently of cardiac disease severity. Chronic inflammation may be an explanation for this association, because inflammation plays an important role in the pathogenesis of acute ischemic stroke and dementia. In the present study, we selected five candidate biomarkers for Chagas disease: interleukin-6, membrane metalloproteinase-9, tissue inhibitor of metalloproteinase-1 (TIMP1), orosomucoid, and neprilysin. We sought to determine if mean levels of proinflammatory biomarkers are higher in patients with heart failure (HF) associated with Chagas disease when compared with other etiologies of HF. Patients were consecutively enrolled from subspecialty HF outpatient clinics at two university-based hospitals. Serum biomarker levels from blood samples were analyzed by ELISA. Severity of HF on echocardiography was worse in non-CD when compared with CD patients. No significant difference was observed in the levels of candidate biomarkers between the CD and non-CD groups. We found a significantly 2.2 ng/mL higher level of TIMP1 in CD when compared with non-CD patients with HF after adjustment for age and gender (95% confidence interval = 0.1 to 4.5, P = 0.037). In patients with heart failure, serum TIMP1 is increased in Chagas patients despite a lower myocardial disease severity on echocardiography when compared with non-Chagas patients. TIMP1 is probably one of multiple mediators of inflammatory injury.

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Abstract 19597: Impact of Hyperglycemia on the Exercise Pressor Reflex in Nondiabetic Patients With Heart Failure

Circulation ◽

10.1161/circ.132.suppl_3.19597 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Karel Rodriguez Milian ◽

Katarzyna Barecka ◽

Ross W May ◽

Tomasz Krauze ◽

Andrzej Wykretowicz ◽

...

Keyword(s):

Heart Failure ◽

Repeated Measures ◽

Analysis Of Covariance ◽

Glycemic Status ◽

Autonomic Dysregulation ◽

Exercise Pressor Reflex ◽

Significant Difference ◽

Patients With Heart Failure ◽

Pressor Reflex ◽

And Gender

Introduction: The HR and BP responses to exercise (exercise pressor reflex, EPR) predict adverse clinical events in patients with Heart Failure (HF). Although studies have shown that hyperglycemia may induce cardiovascular autonomic dysregulation, the association between glycemic status and EPR in HF patients is poorly understood. Hypothesis: Hyperglycemia would be accompanied by altered EPR after the 6-minute walk test (6MWT) in nondiabetic HF patients. Methods: The HR and BP (SBP and DBP) responses to 6MWT were evaluated in 215 HF ambulatory patients aged 62.4 ± 9.4 (M ± SD) years old before (BASE), immediately after (P0), 1 minute after (P1) and 3 minutes after exercise (P3). Patients were assigned to one of two groups based on their 2-hours post meal (breakfast) glycemia into normoglycemic (<140mg/dl; NG; n = 173) and hyperglycemic (HG; n =42). Results: To compare the HR and BP responses to the 6MWT between the groups a 4 X 2 ([BASE X P0 X P1 X P3] X [NG x HG]) repeated measures analysis of covariance using least significant difference as alpha adjustment that controlled for weight and gender were conducted. Significant (P<0.05) time-by-group interactions occurred for HR, SBP, and DBP such that HR at P0, SBP at BASE, P1 and P3 and DBP at P1 and P3 were higher in the HG group compared to the NG. In addition, we found that SBP response to exercise was blunted where as DBP remained elevated at P1 and P3 in HG group only (see Figure 1). Conclusions: These results demonstrate that post-meal hyperglycemia evokes an abnormal EPR in patients with HF. Such effects might be caused by a hyperglycemia-induced impaired autonomic dysregulation. Future attention should be given at the patient’s glycemic status prior to using an exercise test as it significantly contributes to the EPR.

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Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: Correlation between antibody titers and development of cardiac disease severity

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0005796 ◽

2017 ◽

Vol 11 (7) ◽

pp. e0005796 ◽

Cited By ~ 8

Author(s):

Ingebourg Georg ◽

Alejandro Marcel Hasslocher-Moreno ◽

Sergio Salles Xavier ◽

Marcelo Teixeira de Holanda ◽

Eric Henrique Roma ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Disease Severity ◽

Chagas Disease ◽

Antibody Production ◽

Cardiac Disease ◽

Antibody Titers ◽

Chronic Chagas Disease

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Abstract 065: Cardiac Fibrosis and Heart Failure Caused by DsRed Tetramers Involves the Induction of Tissue Inhibitor of Metalloproteinase-1

Circulation Research ◽

10.1161/res.113.suppl_1.a065 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Tsung-Hsien Chen ◽

Shan-Wen Liu ◽

Mei-Ru Chen ◽

Kurt M Lin

Keyword(s):

Heart Failure ◽

Cardiac Fibrosis ◽

Fluorescent Protein ◽

Early Stage ◽

Transglutaminase 2 ◽

Underlying Mechanism ◽

Tissue Inhibitor Of Metalloproteinase ◽

Tissue Inhibitor ◽

Cardiac Tissues ◽

Cardiac Symptoms

Whereas aggregation of intracellular proteins was linked to the initiation of cardiac myopathy, the sequence of participating events, including myocyte apoptosis, autophagy, necrosis and fibrosis as the underlying mechanisms leading to heart failure, was not clear. Green fluorescent protein (GFP) and its derivatives induced cardiac dysfunction in mice when expressed in high quantity; however, the mechanism underlying the aggregation of fluorescent protein leading to heart failure remains unexplored.We created a transgenic mouse with switchable expression of the GFP monomer or the expression of DsRed, a red fluorescent protein (RFP) tetramer that tends to aggregate into a large protein complex. GFP mice were free of cardiac symptoms; in contrast, RFP mice with homozygous DsRed alleles developed myocyte necrosis, carditis, ventricular hypertrophy and fibrosis, left atrium thrombosis, dilated heart failure and death at the age of approximately five months. The hemizygote mice displayed similar symptoms at a later age. The expression of the microtubule-associated protein 1 light chain 3 cleaved isoform II (LC3 II) and transglutaminase 2, and the expression of many myopathy- and fibrosis-related genes were significantly induced in the hearts of two-month-old RFP mice. Together with the findings of increased autophagosomes, lysosomes and dysfunctional mitochondria, these results suggest a marked induction of myocyte autophagy and fibrosis as the main underlying mechanism of heart failure in RFP mice. Interestingly, apoptosis was not elevated in RFP hearts. One of the most up-regulated genes in the early stage RFP heart was the tissue inhibitor of matrix metalloproteinases type 1 (TIMP-1), corroborating the role of TIMP-1 in cardiac remodeling and anti-apoptotic activity. The heart-origin of the morbidity in RFP mice was confirmed by expressing DsRed tetramers specifically in cardiac tissues, and the same phenotypes as in RFP mice were observed. In summary, in cardiac myocytes under the stress of protein aggregation, strong induction of TIMP-1 and down-regulation of MMP activity may play a significant role in enhancing the synthesis of extracellular matrix, resulting in fibrosis and heart failure.

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The Effect of an Educational Plan Based on the Roy Adaptation Model for Fatigue and Activities of Daily Living of Patients with Heart Failure Disease

Ethiopian Journal of Health Sciences ◽

10.4314/ejhs.v30i4.11 ◽

2020 ◽

Vol 30 (4) ◽

Author(s):

Mahdieh Abdolahi ◽

Mohammad Mahdi Doustmohamadi ◽

Hojjat Sheikhbardsiri

Keyword(s):

Heart Failure ◽

Intervention Group ◽

Nursing Intervention ◽

Daily Activities ◽

Control Group ◽

Roy Adaptation Model ◽

Educational Plan ◽

Significant Difference ◽

Patients With Heart Failure ◽

Adaptation Model

BACKGROUND: Cardiac failure is one of the most common chronic diseases with high rate of morbidity and mortality. Fatigue and decreased ability to perform daily activities are of the most common complications of this disease. The purpose of this study was to determine the effect of an educational plan based on Roy adaptation model on fatigue and daily activities in patients with heart failure.METHODS: This experimental study was performed on 60 heart failure patients admitted in two educational hospitals supervised by the Kerman University of Medical Sciences in 2019. Sample was randomly assigned into two intervention and control groups. The intervention group received the care plan through a face-toface and group training program in 6 sessions at one month. Interval followed by a follow-up period for 4 weeks later. Fatigue level was calculated based on piper fatigue scale, and daily activities were calculated by Barthes scale.RESULTS: The finding indicated that there was a significant difference between the two groups (control and intervention) after the intervention. The result showed that the intervention group had significantly lower mean scores in fatigue and higher mean scores in daily activities compared to the control group after intervention P ≤ .05. There was a significant relationship between fatigue and daily activities of life with frequency of hospitalization and duration of disease in both groups, P ≤ .05.CONCLUSION: Implementation of Roy model-based education program as a low-cost, effective, and non-aggressive nursing intervention can reduce fatigue, and improve daily activities in patients with heart failure.

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The effect of educational intervention based on Pender's health promotion model on quality of life and health promotion in patients with heart failure: an experimental study

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02294-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hossein Habibzadeh ◽

Akram Shariati ◽

Farshad Mohammadi ◽

Salman Babayi

Keyword(s):

Quality Of Life ◽

Heart Failure ◽

Health Promotion ◽

Intervention Group ◽

Health Promotion Model ◽

Significant Difference ◽

Patients With Heart Failure ◽

Health Promoting ◽

Pender's Health Promotion Model

Abstract Background Heart failure is a common and chronic heart condition with high prevalence and mortality rates. This debilitating disease as an important predictor of health outcomes is directly related to patients' quality of life. Given that one of the main goals of heart failure treatment is to promote patients' quality of life and health status, conducting effective nursing interventions seems to be necessary in this regard. Therefore, the present study aimed to determine the effect of educational intervention based on Pender's health promotion model on quality of life and health promotion in patients with heart failure. Methods This is an experimental study in which a total of 80 patients with heart failure were recruited and randomly allocated to two groups of intervention and control (n = 40 in each group). The educational program was designed based on Pender's health promotion model and then provided for the patients in the intervention four subgroups (10 person in each group) during six sessions. Data were collected at three time-points of before, immediately after, and three months after the intervention using a demographic questionnaire, the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and the Health-Promoting Lifestyle Profile II (HPLP-II). Data were then analyzed using SPSS Statistics for Windows, version 17.0 (SPSS Inc., Chicago, Ill., USA) and p value less than 0.05 was taken as statistically significant. Results Based on the results of the present study, no statistically significant difference was shown in terms of demographic characteristics between the two groups. It was also indicated that there was a statistically significant difference in the mean scores of all dimensions of quality of life (except in the physical dimension) between the two groups so that the overall mean score of quality of life increased significantly in the intervention group after the intervention (p < .05). Moreover, there were significant increases in the mean scores of health-promoting behaviors (except in the domain of physical activity) in the intervention group compared to the control group (p < .05) after intervention. Conclusions This study demonstrates a trend that Pender's health promotion model is effective in improving the quality of life of patients with heart failure except of the physical dimension, and strengthening their health-promoting behaviors in all dimensions except of the physical activity dimension.

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Oral Metolazone Versus Intravenous Chlorothiazide as an Adjunct to Loop Diuretics for Diuresis in Acute Decompensated Heart Failure With Reduced Ejection Fraction

Hospital Pharmacy ◽

10.1177/0018578718795855 ◽

2018 ◽

Vol 54 (6) ◽

pp. 351-357 ◽

Cited By ~ 1

Author(s):

Brian C. Bohn ◽

Rim M. Hadgu ◽

Hannah E. Pope ◽

Jerrica E. Shuster

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Acute Decompensated Heart Failure ◽

Decompensated Heart Failure ◽

Oral Formulation ◽

Loop Diuretics ◽

Reduced Ejection Fraction ◽

Significant Difference ◽

Patients With Heart Failure ◽

Total Urine

Background: Thiazide diuretics are often utilized to overcome loop diuretic resistance when treating acute decompensated heart failure (ADHF). In addition to a large cost advantage, several pharmacokinetic advantages exist when administering oral metolazone (MTZ) compared with intravenous (IV) chlorothiazide (CTZ), yet many providers are reluctant to utilize an oral formulation to treat ADHF. The purpose of this study was to compare the increase in 24-hour total urine output (UOP) after adding MTZ or CTZ to IV loop diuretics (LD) in patients with heart failure with reduced ejection fraction (HFrEF). Methods and Results: From September 2013 to August 2016, 1002 patients admitted for ADHF received either MTZ or CTZ in addition to LD. Patients were excluded for heart failure with preserved ejection fraction (HFpEF) (n = 469), <24-hour LD or UOP data prior to drug initiation (n = 129), or low dose MTZ/CTZ (n = 91). A total of 168 patients were included with 64% receiving CTZ. No significant difference was observed between the increase in 24-hour total UOP after MTZ or CTZ initiation (1458 [514, 2401] mL vs 1820 [890, 2750] mL, P = .251). Conclusions: Both MTZ and CTZ similarly increased UOP when utilized as an adjunct to IV LD. These results suggest that while thiazide agents can substantially increase UOP in ADHF patients with HFrEF, MTZ and CTZ have comparable effects.

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P3453Gender difference in impact of ischemic heart disease on long-term outcome in patients with heart failure reduced ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehz745.0326 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

H J Kim ◽

M A Kim ◽

D I Lee ◽

H L Kim ◽

D J Choi ◽

...

Keyword(s):

Heart Failure ◽

Clinical Outcomes ◽

Survival Rates ◽

Free Survival ◽

Reduced Ejection Fraction ◽

Clinical Events ◽

Significant Difference ◽

Patients With Heart Failure

Abstract Background Ischemic heart disease (IHD) is a major underlying etiology in patients with heart failure (HF). Although the impact of IHD on HF is evolving, there is a lack of understanding of how IHD affects long-term clinical outcomes and uncertainty about the role of IHD in determining the risk of clinical outcomes by gender. Purpose This study aims to evaluate the gender difference in impact of IHD on long-term clinical outcomes in patients with heart failure reduced ejection fraction (HFrEF). Methods Study data were obtained from the nationwide registry which is a prospective multicenter cohort and included patients who were hospitalized for HF composed of 3,200 patients. A total of 1,638 patients with HFrEF were classified into gender (women 704 and men 934). The primary outcome was all-cause death during follow-up and the composite clinical events of all-cause death and HF readmission during follow-up were also obtained. HF readmission was defined as re-hospitalization because of HF exacerbation. Results 133 women (18.9%) were died and 168 men (18.0%) were died during follow-up (median 489 days; inter-quartile range, 162–947 days). As underlying cause of HF, IHD did not show significant difference between genders. Women with HFrEF combined with IHD had significantly lower cumulative survival rate than women without IHD at long-term follow-up (74.8% vs. 84.9%, Log Rank p=0.001, Figure 1). However, men with HFrEF combined with IHD had no significant difference in survival rate compared with men without IHD (79.3% vs. 83.8%, Log Rank p=0.067). After adjustment for confounding factors, Cox regression analysis showed that IHD had a 1.43-fold increased risk for all-cause mortality independently only in women. (odds ratio 1.43, 95% confidence interval 1.058–1.929, p=0.020). On the contrary to the death-free survival rates, there were significant differences in composite clinical events-free survival rates between patients with HFrEF combined with IHD and HFrEF without IHD in both genders. Figure 1 Conclusions IHD as predisposing cause of HF was an important risk factor for long-term mortality in women with HFrEF. Clinician need to aware of gender-based characteristics in patients with HF and should manage and monitor them appropriately and gender-specifically. Women with HF caused by IHD also should be treated more meticulously to avoid a poor prognosis. Acknowledgement/Funding None

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Pulse-synchronous sympathetic burst power as a new index of sympathoexcitation in patients with heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00252.2003 ◽

2004 ◽

Vol 287 (4) ◽

pp. H1821-H1827 ◽

Cited By ~ 4

Author(s):

Yoshitaka Oda ◽

Hidetsugu Asanoi ◽

Hiroshi Ueno ◽

Kunihiro Yamada ◽

Shuji Joho ◽

...

Keyword(s):

Heart Failure ◽

Sympathetic Nerve ◽

Sympathetic Activity ◽

Sympathetic Nerve Activity ◽

Class Ii ◽

Plasma Norepinephrine ◽

Class Iii ◽

Nerve Activity ◽

Significant Difference ◽

Patients With Heart Failure

The upper limit of incidence of muscle sympathetic neural bursts can lead to underestimation of sympathetic activity in patients with severe heart failure. This study aimed to evaluate the pulse-synchronous burst power of muscle sympathetic nerve activity (MSNA) as a more specific indicator that could discriminate sympathetic activity in patients with heart failure. In 54 patients with heart failure, the pulse-synchronous burst power at the mean heart rate was quantified by spectral analysis of MSNA. Thirteen patients received a central sympatholytic agent (guanfacine) for 5 days to validate the feasibility of this new index. Both burst incidence and plasma norepinephrine level showed no significant difference between patients in New York Heart Association functional class III (94 ± 6 per 100 heartbeats and 477 ± 219 pg/ml, respectively) and class II (79 ± 14 per 100 heartbeats and 424 ± 268 pg/ml, respectively). In contrast, the burst power was useful for discriminating patients in class III from those in class II (61 ± 8% vs. 39 ± 10%; P < 0.05). Inhibition of sympathetic nerve activity by guanfacine was more sensitively reflected by the change of burst power (−36 ± 25%) than by that of burst incidence (−12 ± 14%; P < 0.001). The sympathetic burst power reflects both burst frequency and amplitude independently of the absolute values and provides a sensitive new index for interindividual comparisons of sympathetic activity in patients with heart failure.

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0602 Daytime Sleepiness in Heart Failure with Preserved Versus Reduced Ejection Fraction

SLEEP ◽

10.1093/sleep/zsaa056.599 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A230-A230

Author(s):

S G Schütz ◽

A Nguyen-Phan ◽

M Konerman ◽

S Hummel ◽

R D Chervin

Keyword(s):

Heart Failure ◽

Sleep Apnea ◽

Ejection Fraction ◽

Daytime Sleepiness ◽

Diastolic Heart Failure ◽

Apnea Hypopnea Index ◽

Central Apnea ◽

Reduced Ejection Fraction ◽

Significant Difference ◽

Patients With Heart Failure

Abstract Introduction Sleep apnea is common in patients with heart failure, though often not associated with significant daytime sleepiness in heart failure with reduced ejection fraction (HFrEF). The clinical presentation of sleep apnea in patients who have heart failure with borderline or preserved ejections fraction (HFbEF and HFpEF, respectively) is not well characterized. Methods Eighty patients with heart failure were identified retrospectively in data from University of Michigan Sleep Disorders Laboratories. Heart failure was categorized as heart failure with reduced ejection fraction (HFrEF)/systolic heart failure, heart failure with borderline ejection fraction (HFbEF) or heart failure with preserved ejection fraction (HFpEF)/diastolic heart failure. Clinical information and Epworth Sleepiness Scale (ESS) scores were extracted from medical records. A subset of subjects underwent a diagnostic polysomnogram. ANOVA was used to compare clinical characteristics in subjects with different heart failure types. Results ESS scores trended higher in 49 subjects with HFpEF (ESS mean 10.9±4.7 [sd]) compared to 9 with HFbEF (ESS 8.0±3.4) and 22 with HFrEF (ESS 8.4±5.0) (p=0.058). Among the 40 subjects who underwent diagnostic polysomnography, no statistically significant difference emerged in apnea-hypopnea index between subjects with HFpEF, HFbEF, and HFrEF (p=0.43). No significant differences emerged for the central apnea index (p=0.16), despite magnitudes of discrepancy that suggested a larger sample size might show different results CAI in participants with HFrEF showed a mean of 9.0±14.6/h, compared to 0.1±0.1/h in HFbEF and 3.1±6.3/h in HFpEF. Conclusion Among these patients with HFpEF, HFbEF, and HFrEF, subjects with HFpEF showed a trend towards increased subjective daytime sleepiness, though overall apnea and central apnea severity did not differ between groups. Further examination of clinical phenotypes in larger cohorts may help guide care in heterogeneous heart failure populations. Support National Institutes of Health grant NS107158

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