The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction.

Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78-1.85 ng/dL) and triiodothyronine (T3, 76-190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 50% and (a) E/e' ratio > 15, or (b) E/e' ratio of 8-15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01-1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.

Correlations of Serum Lipid Parameters and Atherogenic Indices With Left Ventricular Diastolic Dysfunction Among Apparently Healthy Patients With Type 2 Diabetes Mellitus: A Multicenter In-Hospital Cross-Sectional Study.

Background: In adolescents with Type 1 diabetes, lipid ratios are predictors of left ventricular diastolic dysfunction (LVDD). However, whether this also applies to adults with Type 2 Diabetes Mellitus (T2DM) is unclear. This study is aimed at assessing the correlations of serum lipid parameters and atherogenic indices with LVDD in patients with T2DM. Methods: This cross-sectional study included 203 patients with T2DM aged 59.9 ± 13.6 years (111 males, sex ratio: 1 : 2 in favor of males) from eight randomly selected urban hospitals. Demographic information was collected, an anthropometric assessment was performed, and blood pressure was measured. Fasting blood samples were obtained to assess total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), glucose, and glycated hemoglobin. The atherogenic index of plasma (AIP), Castelli Risk Index I (CRI-I), Castelli Risk Index II (CRI-II), atherogenic coefficient, and non-HDL-C were determined using specific formulas. Diastolic function was assessed using echocardiography as per the 2016 updated guidelines of the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI). Results: Approximately 47.8% of the participants had LVDD. Compared with participants with normal diastolic function, those with LVDD were more likely to be older than 55 years (p < 0.001), tended to have obesity (p = 0.045), had a higher risk of developing dyslipidemia (p = 0.041), and higher AIP and CRI-II (p < 0.05) levels while having similar low HDL-C and hypertriglyceridemia frequencies. In the multivariate model adjusting for age, high AIP (adjusted odds ratio [aOR], 3.37; 95% confidence interval [CI], 1.22-5.34) and high CRI-II (aOR: 3.80; 95% CI: 2.25-6.35) were independent determinants of LVDD. Conclusions: These results highlight the importance of considering atherogenic indices, primarily AIP and CRI-II in the management of T2DM patients. High AIP and high CRI-II could serve as surrogate markers of LVDD, an early cardiovascular manifestation in patients with T2DM.

Additive effect of admission hyperglycemia on left ventricular stiffness in patients following acute myocardial infarction verified by CMR tissue tracking.

BACKGROUND: Stress hyperglycemia occurs frequently in patients following acute myocardial infarction (AMI) and may aggravate myocardial stiffness, but relevant evidence is still lacking. Accordingly, this study aimed to examine the impact of admission stress hyperglycemia on left ventricular (LV) myocardial deformation in patients following AMI. METHODS: A total of 171 patients with first AMI (96 with normoglycemia and 75 with hyperglycemia) underwent cardiac magnetic resonance (CMR) examination were included. AMI patients were classified according to admission blood glucose level (aBGL): < 7.8 mmol/L (n = 96), 7.8-11.1 mmol/L (n = 41) and ≥ 11.1 mmol/L (n = 34). LV strains, including global radial/circumferential/longitudinal peak strain (PS)/peak systolic strain rate (PSSR)/peak diastolic strain rate (PDSR), were measured and compared between groups. Further, subgroup analyses were separately conducted for AMI patients with and without diabetes. Multivariate analysis was employed to assess the independent association between aBGL and LV global PS in AMI patients. RESULTS: LV global PS, PSSR and PDSR were decreased in radial, circumferential and longitudinal directions in hyperglycemic AMI patients compared with normoglycemic AMI patients (all P < 0.05). These differences were more obvious in patients with diabetes than those without diabetes. AMI patients with aBGL between 7.8 and 11.1 mmol/L demonstrated significant decreased radial and longitudinal PS, radial PSSR, and radial and longitudinal PDSR than those with aBGL < 7.8 mmol/L (all P < 0.05). AMI patients with aBGL ≥ 11.1 mmol/L showed significantly decreased PS, PSSR and PDSR in all three directions than those with aBGL < 7.8 mmol/L, and decreased longitudinal PSSR than those with aBGL between 7.8 and 11.1 (all P < 0.05). Further, aBGL was significantly and independently associated with radial (ß = - 0.166, P = 0.003) and longitudinal (ß = 0.143, P = 0.008) PS. CONCLUSIONS: Hyperglycemia may exacerbate LV myocardial stiffness in patients experienced first AMI, leading to reduction in LV strains. aBGL was an independent indicator of impaired LV global PS in AMI patients. Blood glucose monitoring is more valuable for AMI patients with diabetes.

AST/ALT Ratio as an indicator of functional severity in chronic heart failure with reduced left ventricular ejection fraction: A prospective cross-sectional study.

OBJECTIVE: The study was carried out to evaluate the role of the AST (Aspartate transaminase)/ALT (Alanine transaminase) ratio as an indicator of the functional severity in people with chronic heart failure (CHF) with reduced left ventricular ejection fraction. METHODS: A prospective cross-sectional study was conducted in a tertiary care centre in South India among the individuals who had left ventricular ejection fraction (LVEF) of ≤40 %. The study period was between January 2021 and December 2021. Consecutive patients with the criteria were enrolled in the study. Study participants were grouped based on their AST/ALT ratio value (ratio<1 and ratio≥1). RESULTS: In present study of 100 participants, there was a statistically significant difference between two groups with respect to ALT, AST/ALT ratio, and ALP (Alkaline phosphatase). There was a significant correlation between the APRI (AST to platelet ratio index) and FIB-4 (Fibrosis-4) with AST/ALT ratio. Diagnostic analysis of AST/ALT ratio to predict the severity of CHF with reduced EF, the area under the curve (AUC) was 0.547 (p-value = 0.5654) with a 95 % confidence interval of 0.299-0.795 with an optimal cut-off value of 0.6, sensitivity of 96.70 %, and specificity of 33.33 %. CONCLUSION: The AST/ALT ratio is increased in patients with CHF patients with reduced left ventricular ejection fraction. It is a simple predictor of left ventricular dysfunction in patients with heart failure with reduced ejection fraction.

Correlation between the triglyceride-glucose index and left ventricular global longitudinal strain in patients with chronic heart failure: a cross-sectional study.

BACKGROUND: Left ventricular global longitudinal strain (GLS) holds greater diagnostic and prognostic value than left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. The triglyceride-glucose (TyG) index serves as a reliable surrogate for insulin resistance (IR) and is strongly associated with several adverse cardiovascular events. However, there remains a research gap concerning the correlation between the TyG index and GLS among patients with chronic heart failure (CHF). METHOD: 427 CHF patients were included in the final analysis. Patient demographic information, along with laboratory tests such as blood glucose, lipids profiles, and echocardiographic data were collected. The TyG index was calculated as Ln [fasting triglyceride (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. RESULTS: Among CHF patients, GLS was notably lower in the higher TyG index group compared to the lower TyG index group. Following adjustment for confounding factors, GLS demonstrated gradual decrease with increasing TyG index, regardless of the LVEF level and CHF classification. CONCLUSION: Elevated TyG index may be independently associated with more severe clinical left ventricular dysfunction in patients with CHF.

Association of lipids and inflammatory markers with left ventricular wall thickness in patients with bipolar disorder.

BACKGROUND: Individuals with bipolar disorder (BD) face a high risk of heart failure and left ventricular (LV) dysfunction. Despite strong evidence that high LV relative wall thickness (RWT) is a risk marker for heart failure, few studies have evaluated LV RWT and aggravating factors in individuals with BD. METHODS: We recruited 104 participants (52 patients with BD and 52 age- and sex-matched mentally healthy controls) to undergo echocardiographic imaging and biochemistry, high-sensitivity C-reactive protein (hs-CRP), and blood cell count measurements. LV RWT was estimated using the following equation: (2 × LV posterior wall end-diastolic thickness)/LV end-diastolic diameter. Clinical data were obtained through interviews and chart reviews. RESULTS: The BD group exhibited a significantly greater LV RWT (Cohen's d = 0.53, p = 0.003) and a less favorable mitral valve E/A ratio (Cohen's d = 0.54, p = 0.023) and LV global longitudinal strain (Cohen's d = 0.57, p = 0.047) than did the control group. Multiple linear regression revealed that in the BD group, serum triglyceride levels (ß = 0.466, p = 0.001), platelet-to-lymphocyte ratios (ß = 0.324, p = 0.022), and hs-CRP levels (ß = 0.289, p = 0.043) were all significantly and positively associated with LV RWT. LIMITATIONS: This study applied a cross-sectional design, meaning that the direction of causation could not be inferred. CONCLUSIONS: Patients with BD are at a risk of heart failure, as indicated by their relatively high LV RWT. Lipid levels and systemic inflammation may explain this unfavorable association.

Association of 1,25 dihydroxyvitamin D with left ventricular hypertrophy and left ventricular diastolic dysfunction in patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.

Gut microbiota, blood metabolites, and left ventricular diastolic dysfunction in US Hispanics/Latinos.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is an important precursor of heart failure (HF), but little is known about its relationship with gut dysbiosis and microbial-related metabolites. By leveraging the multi-omics data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a study with population at high burden of LVDD, we aimed to characterize gut microbiota associated with LVDD and identify metabolite signatures of gut dysbiosis and incident LVDD. RESULTS: We included up to 1996 Hispanic/Latino adults (mean age: 59.4 years; 67.1% female) with comprehensive echocardiography assessments, gut microbiome, and blood metabolome data. LVDD was defined through a composite criterion involving tissue Doppler assessment and left atrial volume index measurements. Among 1996 participants, 916 (45.9%) had prevalent LVDD, and 212 out of 594 participants without LVDD at baseline developed incident LVDD over a median 4.3 years of follow-up. Using multivariable-adjusted analysis of compositions of microbiomes (ANCOM-II) method, we identified 7 out of 512 dominant gut bacterial species (prevalence > 20%) associated with prevalent LVDD (FDR-q < 0.1), with inverse associations being found for Intestinimonas_massiliensis, Clostridium_phoceensis, and Bacteroide_coprocola and positive associations for Gardnerella_vaginali, Acidaminococcus_fermentans, Pseudomonas_aeruginosa, and Necropsobacter_massiliensis. Using multivariable adjusted linear regression, 220 out of 669 circulating metabolites with detection rate > 75% were associated with the identified LVDD-related bacterial species (FDR-q < 0.1), with the majority being linked to Intestinimonas_massiliensis, Clostridium_phoceensis, and Acidaminococcus_fermentans. Furthermore, 46 of these bacteria-associated metabolites, mostly glycerophospholipids, secondary bile acids, and amino acids, were associated with prevalent LVDD (FDR-q < 0.1), 21 of which were associated with incident LVDD (relative risk ranging from 0.81 [p = 0.001, for guanidinoacetate] to 1.25 [p = 9 × 10-5, for 1-stearoyl-2-arachidonoyl-GPE (18:0/20:4)]). The inclusion of these 21 bacterial-related metabolites significantly improved the prediction of incident LVDD compared with a traditional risk factor model (the area under the receiver operating characteristic curve [AUC] = 0.73 vs 0.70, p = 0.001). Metabolite-based proxy association analyses revealed the inverse associations of Intestinimonas_massilliensis and Clostridium_phoceensis and the positive association of Acidaminococcus_fermentans with incident LVDD. CONCLUSION: In this study of US Hispanics/Latinos, we identified multiple gut bacteria and related metabolites linked to LVDD, suggesting their potential roles in this preclinical HF entity. Video Abstract.

Association between the triglyceride-glucose index and subclinical left ventricular systolic dysfunction in obese patients.

BACKGROUND: The association between the triglyceride-glucose (TyG) index and subclinical left ventricular (LV) systolic dysfunction in obese patients remains unclear. This study aimed to investigate the relationship between the TyG index and LV global longitudinal strain (GLS) in obese patients. METHODS: A total of 1028 obese patients from January 2019 to January 2024 were included in the present study. Clinical parameters and biochemical and echocardiographic data were obtained from the participants. LV GLS was obtained from the GE EchoPAC workstation for evaluating subclinical LV function. The TyG index was calculated as Ln (fasting TG [mg/dL] × fasting glucose [mg/dL]/2). LV GLS was compared between obese patients with a high TyG index and those with a low TyG index. RESULTS: Obese patients with a high TyG index had greater incidences of hypertension, diabetes mellitus and hyperlipidaemia. The LV GLS was significantly lower in the high TyG index group than in the low TyG index group (P = 0.01). After adjusting for sex, age, body mass index, heart rate, hypertension, diabetes mellitus, dyslipidaemia, blood urea nitrogen, serum creatinine, LV mass and LV hypertrophy, the TyG index remained an independent risk indicator related to an LV GLS < 20% (OR: 1.520, 95% CI: 1.040 to 2.221; P = 0.031). CONCLUSIONS: We concluded that an increase in the TyG index is independently associated with subclinical LV systolic dysfunction in obese patients.

Association of cardiometabolic and triglyceride-glucose index with left ventricular diastolic function in asymptomatic individuals.

BACKGROUND AND AIMS: Obesity and insulin resistance are associated with left ventricular diastolic dysfunction (LVDD) and increased risk of heart failure. Cardiometabolic index (CMI) and triglyceride glucose (TyG) are new indexes to assess visceral obesity and insulin resistance, respectively. The study aimed to investigate the clinical usefulness of these indexes for identifying LVDD individuals. METHODS AND RESULTS: Overall, 1898 asymptomatic individuals were included in this cross-sectional study. Participants underwent anthropometrics, serum biochemical evaluation, and echocardiography. Multiple linear regression analysis revealed that both indexes were independent determinants of diastolic parameters among females; while for males, CMI and TyG were not associated with A velocity. In the multivariate logistic analysis, the proportion of LVDD in the third and fourth quartiles of CMI remained significantly greater than that in the lowest quartile in females (Q3 vs. Q1: odds ratio (OR) = 2.032, 95% confidence interval (CI): 1.181-3.496; Q4 vs. Q1: OR = 2.393, 95% CI: 1.347-4.249); while in males, the incidence of LVDD was significantly greater only in the fourth quartile. For TyG, the presence of LVDD in the fourth quartile was significantly greater in both genders. The discriminant values between the CMI (AUC: 0.704, 95% CI: 0.668-0.739) and TyG (AUC: 0.717, 95% CI: 0.682-0.752) were similar in females. Both indexes performed better in females than in males to identify LVDD. CONCLUSION: The CMI and TyG might both serve as effective tools to identify LVDD in routine health check-ups in primary care, mainly in females. With simpler parameters, the CMI could be utilized in medically resource-limited areas.

The correlation between serum asprosin and left ventricular diastolic dysfunction in elderly patients with type 2 diabetes mellitus in the community.

AIMS/INTRODUCTION: Serum asprosin is expected to become a screening indicator in early-stage diabetic heart disease. The relationship between serum asprosin and left ventricular diastolic dysfunction (LVDD) was studied in elderly patients with type 2 diabetes mellitus in the community. MATERIALS AND METHODS: A total of 252 elderly patients with type 2 diabetes mellitus were recruited from Zhuoma Community Care Station and Chengbei West Street Community Care Service Center in Changzhi City of Shanxi Province from November 2019 to July 2021. Patients were divided into the LVDD group (n = 195) and the non-LVDD group (n = 57). The t-test, Mann-Whitney U test, and χ2 test were used to compare indicators between the LVDD group and the non-LVDD group. Pearson or Spearman correlation analysis was adopted to evaluate the correlation between serum asprosin and other clinical data. Multivariate logistic regression analysis was applied to analyze the influencing factors on LVDD. RESULTS: Compared with patients without LVDD, patients with LVDD had a higher level of low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), and asprosin, but a lower level of early diastolic movement speed (A) to diastolic movement velocity (E) (E/A). Asprosin was positively associated with waist circumference (WC), body mass index (BMI), creatinine, triglycerides (P < 0.05), and negatively associated with E/A and high density lipoprotein cholesterol HDL-C (P < 0.05). The risk of LVDD increased with elevated asprosin levels after adjustment for age, systolic blood pressure (SBP), BMI, FPG, and LDL-C. Compared with patients in the lowest tertile of serum asprosin (<275.25 pg/mL), a serum level of asprosin between 275.25-355.08 pg/mL [OR (95% CI) is 2.368 (1.169-4.796), P < 0.05] and asprosin >355.08 pg/mL [OR (95% CI) is 2.549 (1.275-5.095), P < 0.05] patients have a higher risk of left ventricular diastolic dysfunction. CONCLUSIONS: Serum asprosin was positively associated with left ventricular diastolic dysfunction, and the risk of LVDD increased significantly with increased serum levels of asprosin.

Correlation of HMGB1, TLR2 and TLR4 with left ventricular diastolic dysfunction in sepsis patients.

Left ventricular diastolic dysfunction (LVDD) is a common consequence of sepsis due to dysregulated inflammatory responses. Here we aim to investigate high mobility group box 1 (HMGB1), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) as serum biomarkers to assess LVDD risk of patients with sepsis. We recruited 120 patients with sepsis, among which 52 had ultrasonically confirmed LVDD and 68 were without LVDD. Blood samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to analyse levels of HMGB1, TLR2 and TLR4 in serum. Multivariate analysis was performed to assess the odds ratio of the serum biomarkers. Spearman's correlation analysis was conducted to evaluate the correlation between the serum biomarkers to B-type natriuretic peptide (BNP) and cardiac troponin I (cTnl) levels and the ratios of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity (E/e' ratios) in ultrasound. Receiver operating curve was used to measure the sensitivity and specificity of HMGB1, TLR2 and TLR4 individually and in combination as diagnostic markers. Elevated HMGB1, TLR2 and TLR4 had significant values in predicting LVDD suggested by high odds ratio (all P < .05). A significant correlation was found between these values and cTnl, the current gold standard for LVDD analysis. HMGB1, TLR2 and TLR4 also showed a high diagnostic sensitivity and specificity in ROC analysis. HMGB1, TLR2 and TLR4 are potentially valuable in predicting LVDD risk among patients with sepsis, providing additional tools with the capability of potentially assisting the clinical management of patients with sepsis.

Correlation of serum ST2 levels with severity of diastolic dysfunction on echocardiography and findings on cardiac MRI in patients with heart failure with preserved ejection fraction.

OBJECTIVE: The aim of the present study was to find a correlation of serum Suppression of tumorigenicity 2 (ST2) levels with severity of diastolic dysfunction on echocardiography and cardiac magnetic resonance imaging (CMRI) in heart failure with preserved ejection fraction (HFpEF) patients. METHODS: Fifty patients aged ≥18 years fulfilling diagnostic criteria for HFpEF were included. ST2 levels, 2D echocardiography and CMRI were performed. Left ventricular ejection fraction, E/A, Septal E/E', left atrial volume index (LAVI), tricuspid regurgitation (TR), assessment of diastolic dysfunction, T1 mapping in milliseconds and late gadolinium enhancement (LGE) in percentage were noted. The primary outcome measure was to study correlation of ST2 levels with severity of diastolic dysfunction, whereas the secondary outcome measures were to study correlation of ST2 levels with native T1 mapping and LGE on CMRI. RESULTS: ST2 levels showed statistically significant and positive correlation with E/E' (r = 0.837), peak TR velocity (r = 0.373), LAVI (r = 0.74), E/A (r = 0.420), and T1 values in milliseconds (r = 0.619). There was no statistically significant correlation between ST2 level and LGE in % (r = 0.145). The median ST2 levels in patients with E/E' > 14 and E/E' ≤ 14 were 110.8 and 36.1 respectively (p-value < 0.05). The mean ST2 levels were significantly higher in patients who had diastolic dysfunction grade III (126.4) and New York Heart Association class IV (133.3). CONCLUSIONS: Evaluation of ST2 adds important information to support the diagnosis of left ventricular diastolic dysfunction in patients with HFpEF.

Association between brain natriuretic peptide and cardiac dysfunction in hypertensive pregnancy disorders.

OBJECTIVE: The aim of this work is to identify the correlation between serum brain natriuretic peptide (BNP) and left ventricle (LV) systolic and diastolic function in hypertensive pregnancy disorders (HPD) through echocardiographic parameters. STUDY DESIGN: Eighty-seven pregnant patients were included, 23 with normotensive pregnancy (NP), 28 with gestational hypertension (GH) and 36 with preeclampsia (PE). Conventional 2D echocardiography was used to evaluate systolic and diastolic function such as E/a, E/e', LV mass index, LV ejection fraction, as well as left atria (LA) diameters, LA indexed volume, LV strain and LA strain (LAS). Brain natriuretic levels (BNP) blood levels were also determined. MAIN OUTCOME MEASURES: The serum levels of BNP were higher in patients with PE [median (interquartile range, IQR)] 189 (142-215) pg/ml and GH 105 (46-162) pg/ml compared to NP 23 (9-33) pg/ml, (p = 0.001). BNP levels had a negative correlation with LAS (Rho = -0.79, p < 0.001). Preeclampsia patients had lower LAS [median (IQR)] 22% (20%-24%) compared to the GH group 23% (20%-24%) and NP 35% (34% -35%), p = 0.001. Classification and Regression Trees multivariate analysis found patterns that define trends to form mutually excluding homogeneous groups such as: a) First parameter that separates 2 groups is septal e > 8.2 or < 8.2b), BNP serum levels above 89 pg/ml, and c) LAS increases the discriminatory performance to detect and define the diastolic dysfunction or not. CONCLUSIONS: At least one third of women with HPD had moderate diastolic dysfunction. The degree of diastolic dysfunction was negatively correlated with serum BNP levels and severity of HPD. LAS increase discriminatory performance to identify diastolic dysfunction in HPD.

In Vivo Cardiotoxic Potential of Micrurus frontalis Venom.

In the present study, we investigated the cardiotoxic potential of Micrurus frontalis venom. Twelve guinea pigs (Cavia porcellus) were distributed in two groups (n = 6), named control and envenomed. Control groups received 0.2 ml of PBS/BSA, while envenomed group received 0.2 ml of the same solution containing 450 µg/kg of M. frontalis venom. Both were intramuscular injections. Electrocardiography, echocardiogram, blood count, and serum biochemistry were performed before and 2 h after inoculation. Necropsy was performed, and histological and ultrastructural analysis of the heart were conducted. First clinical signs were presented as early as 18 min after venom inoculation. All poisoned animals presented flaccid paralysis of both hind and forelimbs, followed by fasciculations and respiratory arrythmia. However, the animals did not die in the first 2 h of poisoning. ECG of the poisoned animals revealed severe ventricular arrythmias, corroborated by reduction of both ejection and shortening fractions, increase in CK, CK-MB, troponin, cardiomyocyte degeneration, fragmentation and mitochondrial damage. M. frontalis venom causes severe heart damage, eliciting both morphological and arrhythmogenic effects after only 2 h of envenomation.

Elevated Serum Fibroblast Growth Factor 21 Is Relevant to Heart Failure Patients with Reduced Ejection Fraction.

OBJECTIVE: The aim of this study was to evaluate the roles of fibroblast growth factor 21 (FGF21) in heart failure patients with reduced ejection fraction and its association with Heart Failure with reduced Ejection Fraction (HFrEF). METHODS: The level of FGF21 was measured by enzyme-linked immunosorbent assay (ELISA) in 199 subjects enrolled in this study, including 128 subjects with HFrEF and 71 control subjects. The mean follow-up time was 13.36 months. The left ventricular end-diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) percentage were evaluated by the 2D echocardiography. Serum brain natriuretic peptide (BNP) was measured in the routine clinical laboratory. RESULTS: The serum FGF21 level was evidently higher in patients with HFrEF than in the control group (228.72 ± 24.04 vs. 171.60 ± 12.98, p < 0.001). After 1 year of follow-up, 61 patients (47.66%) with heart failure were readmitted to the hospital, including 8 deaths (13.11%). The AUC of the receiver operating characteristic (ROC) curve for the predictive value of FGF21 for prognosis was 0.964. Kaplan-Meier analysis results showed that there were significant differences in the 1-year mortality and heart failure readmission events between the grouped subjects. A poor prognosis was correlated with the serum level of FGF21, BNP, LVEDD, and LVEF, which was confirmed by the univariate Cox analysis. CONCLUSION: FGF21 was independently associated with an increased risk of mortality and readmission HFrEF patients. Therefore, FGF21 has the potential to be a biomarker for the progression of HFrEF in patients.

Characterization of Circulating and Urinary Biomarkers in the Fontan Circulation and Their Correlation With Cardiac Imaging.

Several circulating biomarkers have been found to play a role in the surveillance and risk stratification of heart failure without congenital heart disease, but these have not been widely studied in patients with single ventricles palliated with a Fontan operation. Imaging predictors of worse outcomes in this population include ventricular dilation and dysfunction. Patients who weighed >30 kg with a Fontan circulation referred for cardiac magnetic resonance imaging were invited to participate in the study. Blood and urine samples were obtained at the time of imaging and multiple conventional and novel biomarkers were measured. A total of 82 patients with a median age of 18 years were enrolled. Among the novel biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T had the strongest correlation with ventricular dilation and dysfunction. NT-ProBNP >100 pg/ml has a sensitivity of 91% for the detection of significant ventricular dilation (end-diastolic volume >120 ml/body surface area1.3) and 82% for detection of ejection fraction <50%. The urinary neutrophil gelatinase-associated lipocalin-2 to creatinine ratio correlated with ejection fraction and estimated glomerular filteration rate. In conclusion, abnormalities in biomarkers of heart failure are common in ambulatory, largely asymptomatic patients with Fontan circulation. NT-ProBNP may serve as a sensitive marker for the identification of patients with significant ventricular dilation or dysfunction. Further work is needed to understand how these easily measured circulating biomarkers may be integrated into clinical care.

Variability in Reassessment of Left Ventricular Ejection Fraction After Myocardial Infarction in the Acute Myocardial Infarction Quality Assurance Canada Study.

Importance: Persistently depressed left ventricular ejection fraction (LVEF) after myocardial infarction (MI) is associated with adverse prognosis and directs the use of evidence-based treatments to prevent sudden cardiac death and/or progressive heart failure. Objective: To assess adherence with guideline-recommended LVEF reassessment and to study the evolution of LVEF over 6 months of follow-up. Design, Setting, and Participants: This was a multicenter cohort study at Canadian academic and community hospitals with on-site cardiac catheterization services. Patients with type 1 acute MI and LVEF less than or equal to 45% during the index hospitalization were enrolled between January 2018 and August 2019 and were followed-up for 6 months. Data analysis was performed from May 2020 to September 2021. Exposures: Baseline clinical factors, in-hospital care and LVEF, and site-specific features. Main Outcomes and Measures: The main outcomes were receipt of repeat LVEF assessment by 6 months and the presence of a persistent LVEF reduction at 2 thresholds: LVEF less than or equal to 40%, prompting consideration of additional medical therapy for heart failure, or LVEF less than or equal to 35%, prompting referral for implanted cardioverter defibrillator in addition to medical therapy. Results: This study included 501 patients (mean [SD] age, 63.3 [13.0] years; 113 women [22.6%]). Overall, 370 patients (73.4%) presented with STEMI, and 454 (90.6%) had in-hospital revascularization. The median (IQR) baseline LVEF was 40% (34%-43%). Of 458 patients (91.4%) who completed the 6-month follow-up, 303 (66.2%; 95% CI, 61.7%-70.5%) had LVEF reassessment, with a range of 46.7% to 90.0% across sites (χ213 = 19.6; P = .11). Participants from community hospitals were more likely than those from academic hospitals to undergo LVEF reassessment (73.6% vs 63.2%; χ21 = 4.50; P = .03), as were those with worse LVEF at baseline. Follow-up LVEF improved by an absolute median (IQR) of 8% (3%-15%). However, 103 patients (34.1%) met the definitions of clinically relevant LVEF reduction, including 52 patients (17.2%) with LVEF less than or equal to 35% and 51 patients (16.9%) with LVEF of 35.1% to 40.0%. Conclusions and Relevance: In this cohort study, approximately 1 in 3 patients with at least mild LVEF reduction after acute MI did not undergo indicated LVEF reassessment within 6 months, suggesting that programs to improve the quality of post-MI care should include measures to ensure that indicated repeat cardiac imaging is performed. In those with follow-up imaging, clinically relevant persistent LVEF reduction was identified in more than one-third of patients.

Effects of canagliflozin on NT-proBNP stratified by left ventricular diastolic function in patients with type 2 diabetes and chronic heart failure: a sub analysis of the CANDLE trial.

BACKGROUND: Identification of the effective subtypes of treatment for heart failure (HF) is an essential topic for optimizing treatment of the disorder. We hypothesized that the beneficial effect of SGLT2 inhibitors (SGLT2i) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) might depend on baseline diastolic function. To elucidate the effects of SGLT2i in type 2 diabetes mellitus (T2DM) and chronic HF we investigated, as a post-hoc sub-study of the CANDLE trial, the effects of canagliflozin on NT-proBNP levels from baseline to 24 weeks, with the data stratified by left ventricular (LV) diastolic function at baseline. METHODS: Patients (n = 233) in the CANDLE trial were assigned randomly to either an add-on canagliflozin (n = 113) or glimepiride treatment groups (n = 120). The primary endpoint was a comparison between the two groups of the changes from baseline to 24 weeks in NT-pro BNP levels, stratified according to baseline ventricular diastolic function. RESULTS: The change in the geometric mean of NT-proBNP level from baseline to 24 weeks was 0.98 (95% CI 0.89-1.08) in the canagliflozin group and 1.07 (95% CI 0.97-1.18) in the glimepiride group. The ratio of change with canagliflozin/glimepiride was 0.93 (95% CI 0.82-1.05). Responder analyses were used to investigate the response of an improvement in NT-proBNP levels. Although the subgroup analyses for septal annular velocity (SEP-e') showed no marked heterogeneity in treatment effect, the subgroup with an SEP-e' < 4.7 cm/s indicated there was an association with lower NT-proBNP levels in the canagliflozin group compared with that in the glimepiride group (ratio of change with canagliflozin/glimepiride (0.83, 95% CI 0.66-1.04). CONCLUSIONS: In the subgroup with a lower LV diastolic function, canagliflozin showed a trend of reduced NT-pro BNP levels compared to that observed with glimepiride. This study suggests that the beneficial effects of canagliflozin treatment may be different in subgroups classified by the severity of LV diastolic dysfunction.

The role of serum and dietary advanced glycation endproducts in relation to cardiac function and structure: The Hoorn Study.

BACKGROUND AND AIMS: This study aims to investigate the relationship of serum and dietary advanced glycation endproducts (AGEs) with cardiac function and structure after eight years of follow-up. METHODS AND RESULTS: We included 370 Hoorn Study participants (aged 66.4 ± 6.1, 47% women). Serum protein-bound AGEs [Nε-(carboxymethyl)lysine, Nε-(carboxyethyl)lysine, and pentosidine], as well as echocardiography to assess left atrium volume index (LAVI), left ventricle ejection fraction (LVEF), and left ventricle mass index (LVMI), were measured at baseline and after 8 years of follow-up. Dietary AGEs [Nε-(carboxymethyl)lysine and Nε-(carboxyethyl)lysine] were estimated at baseline with a validated food-frequency questionnaire and an AGEs database. Increased pentosidine [-1.4% (-2.6;-0.2)] and overall serum AGEs Z-scores over time [-2.1% (-3.8;-0.5)] were associated with decreased LVEF at follow-up, adjusted for confounders. Glucose metabolism status was an effect modifier (P-for-interaction = 0.04). In participants with impaired glucose metabolism, but not type 2 diabetes, increased pentosidine was associated with decreased LVEF [-4.2 (-8.0;-0.3)%]. Higher dietary Nε-(carboxyethyl)lysine [1.9 (0.1; 3.7)%] and overall dietary AGEs Z-scores [2.1 (0.1; 4.2)%] were associated with higher LVEF at follow-up. However, prior cardiovascular disease (CVD) was an effect modifier (P = 0.02). We found a stronger, non-significant, association of higher dietary (carboxyethyl)lysine with higher LVEF at follow-up in participants without CVD [2.3 (-0.1; 4.7)%] compared to participants with CVD [0.6 (-2.1; 3.4)%]. CONCLUSION: Overall serum AGEs were longitudinally associated with impaired systolic function. Future research should focus on including changes in dietary AGEs intake over time and the relation of dietary AGEs with cardiac measures needs to be established in intervention studies using low AGEs diets.