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.

Independent Association of Fatty Liver Index With Left Ventricular Diastolic Dysfunction in Subjects Without Medication.

Nonalcoholic fatty liver disease has been reported to be potentially linked to cardiovascular disease. Fatty liver index (FLI) is a noninvasive and simple predictor of nonalcoholic fatty liver disease. However, little is known about the relationship between FLI and cardiac function, especially in a general population. We investigated the relationships of FLI with echocardiographic parameters in 185 subjects (men/women: 79/106) of the Tanno-Sobetsu Study, a population-based cohort, who were not being treated with any medication and who underwent echocardiography. FLI was negatively correlated with high-density lipoprotein cholesterol and peak myocardial velocity during early diastole (e'; r = -0.342, p <0.001), an index of left ventricular (LV) diastolic function, and ratio of peak mitral velocities during early and late diastole (E/A) and was positively correlated with age, systolic and diastolic blood pressures, creatinine, uric acid, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, ratio of mitral to myocardial early diastolic peak velocity (E/e'), left atrial volume index and LV mass index. No significant correlation was found between FLI and LV ejection fraction. Stepwise multivariable regression analysis showed that FLI was independently and negatively associated with e' after adjustment of age, gender, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, and high-sensitivity C-reactive protein. Conversely, e' was independently and negatively associated with FLI after adjustment of age, gender, systolic blood pressure, and LV ejection fraction. In conclusion, elevated FLI is independently associated with LV diastolic dysfunction in a general population without medication. FLI would be a novel marker of LV diastolic dysfunction as an early sign of myocardial injury.

Elevated Plasma Homocysteine Level Associated with Further Left Ventricular Structure and Function Damages in Type 2 Diabetic Patients: A Three-Dimensional Speckle Tracking Echocardiography Study.

Aims: The aims of this study were to explore the left ventricular (LV) structural remodeling and its risk factors in type 2 diabetes mellitus (T2DM) patients with or without hyperhomocysteinemia (hHcy) and to detect the accompanied LV dysfunction using three-dimensional speckle tracking echocardiography (3DSTE). Methods: There were totally 80 T2DM patients with undamaged LV ejection fraction (≥55%) in this study, 40 of whom were also diagnosed with hHcy as co-morbidity. Forty age- and gender-matched controls were also recruited. The risk factors and corresponding diagnostic values for LV remodeling (LVR) were, respectively, determined using logistic regression and area under the receiver operating characteristic curves (AUC). The 3DSTE was used to measure global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS). Results: The constituent ratio of LV geometry showed significant differences among the study populations (P = 0.01). Compared with the controls, three types of LVR accounted for larger proportion in the two T2DM groups, whereas LV hypertrophy was most prevalent in those with T2DM and hHcy. Glycosylated hemoglobin (HbA1c), total plasma homocysteine (tHcy), and HbA1c plus tHcy were all significant risk factors associated with LVR in T2DM patients (AUC values: 0.741, 0.746 and 0.851, respectively). The patients with T2DM alone had significantly lower GLS and GAS than the controls (both P < 0.05). The patients with T2DM and hHcy had significantly lower GLS, GCS, GAS, and GRS than the controls (all P < 0.001), and also had significantly lower GLS, GCS, and GRS than the patients with T2DM alone (all P < 0.05). Conclusions: The 3DSTE plus conventional echocardiography could be used as an effective supplement for detecting early and occult cardiac damages in T2DM patients with plasma homocysteine at normal or elevated levels.

IGFBP7 and GDF-15, but not P1NP, are associated with cardiac alterations and 10-year outcome in an elderly community-based study.

BACKGROUND: Little is known about the clinical value of Insulin-like growth factor-binding protein-7 (IGFBP7), a cellular senescence marker, in an elderly general population with multiple co-morbidities and high prevalence of asymptomatic cardiovascular ventricular dysfunction. Inflammation and fibrosis are hallmarks of cardiac aging and remodelling. Therefore, we assessed the clinical performance of IGFBP7 and two other biomarkers reflecting these pathogenic pathways, the growth differentiation factor-15 (GFD-15) and amino-terminal propeptide of type I procollagen (P1NP), for their association with cardiac phenotypes and outcomes in the PREDICTOR study. METHODS: 2001 community-dwelling subjects aged 65-84 years who had undergone centrally-read echocardiography, were selected through administrative registries. Atrial fibrillation (AF) and 4 echocardiographic patterns were assessed: E/e' (> 8), enlarged left atrial area, left ventricular hypertrophy (LVH) and reduced midwall circumference shortening (MFS). All-cause and cardiovascular mortality and hospitalization were recorded over a median follow-up of 10.6 years. RESULTS: IGFBP7 and GDF-15, but not P1NP, were independently associated with prevalent AF and echocardiographic variables after adjusting for age and sex. After adjustment for clinical risk factors and cardiac patterns or NT-proBNP and hsTnT, both IGFBP7 and GDF-15 independently predicted all-cause mortality, hazard ratios 2.13[1.08-4.22] and 2.03[1.62-2.56] per unit increase of Ln-transformed markers, respectively. CONCLUSIONS: In a community-based elderly cohort, IGFBP7 and GDF-15 appear associated to cardiac alterations as well as to 10-year risk of all-cause mortality.

Glucose fluctuation accelerates cardiac injury of diabetic mice via sodium-dependent glucose cotransporter 1 (SGLT1).

Recent studies have shown that blood glucose fluctuation is associated with complications of diabetes mellitus (DM). SGLT1 (sodium-dependent glucose cotransporter 1), is highly expressed in pathological conditions of heart, and is expressed in cardiomyocytes induced by high glucose. Herein, we constructed a diabetic mouse model with glucose fluctuation to investigate whether SGLT1 is involved in glucose fluctuation-induced cardiac injury. Echocardiography, histology examination, and TUNEL staining were performed to evaluate cardiac dysfunction and damage. To assess glucose fluctuation-induced oxidative stress, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels were measured. To assess mitochondrial dysfunction, mitochondrial membrane potential (MMP), ATP content, mitochondrial respiratory chain complex activity, and expression of mitochondrial fusion and fission proteins were determined. The results indicated that diabetic mice with glucose fluctuation showed elevation of cardiac SGLT1 expression, left ventricular dysfunction, oxidative stress and mitochondrial dysfunction. Knockdown of SGLT1 could abrogate the effects of glucose fluctuation on cardiac injury. Thus, our study highlighted that SGLT1 plays an important role in glucose fluctuation induced cardiac injury through oxidative stress and mitochondrial dysfunction.

Inflammatory markers in acute myocardial infarction and the correlation with the severity of coronary heart disease.

INTRODUCTION: The inflammatory hypothesis of atherosclerosis is appealing in acute coronary syndromes, but the dynamics and precise role are not established. OBJECTIVES: The study investigates the levels of C reactive protein (CRP), interleukin 1ß (IL-1ß) and stromal-derived factor 1α (SDF-1α) at the time of acute myocardial infarction (AMI) and at 1 and 6 months afterwards, compared with a control group. RESULTS: In the acute phase of AMI, CRP and SDF-1α were significantly higher, while IL-1ß showed lower levels compared with controls. CRP positively correlated with coronary stenosis severity (rho = 0.3, p=.05) and negatively related with left ventricle ejection fraction (LVEF) at 1 month (rho= -0.43, p=.05). IL-1ß weakly correlated with the severity of coronary lesions (rho =0.29, p=.02) and strongly with LVEF (rho= -0.8, p=.05). SDF-1α, slightly correlated with LVEF at 1 month (rho = 0.22, p=.01) and with the severity of coronary atherosclerosis (rho= -0.41, p=.003). CONCLUSIONS: CRP, IL-1ß and SDF-1α have important dynamic in the first 6 months after AMI and CRP and SDF-1α levels correlated with the severity of coronary lesions and LVEF at 1 month after the acute ischaemic event.

Routine use of natriuretic peptides: Lessons from a big data analysis.

BACKGROUND: Natriuretic peptides have broad indications during heart failure and the detection of left ventricular dysfunction in high-risk patients. They can also be used for the diagnosis/management of other cardiac diseases. However, very little is known regarding their use in routine practice. METHODS: We examined all biological tests performed from February 2010 to August 2015 in two districts from the French Brittany, covering 13,653 km2 and including 22,265 physicians. We report the settings and conditions of N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements (the only locally natriuretic peptide available). RESULTS: From a total of 3,606,432 tests requested in 557,650 adult (older than 20 years) patients, only 56,653 (1.6%) included at least one NT-proBNP measurement. NT-proBNP measurements gradually increased, from 9188 in 2011 to 12,938 in 2014 (P < 0.001). Most NT-proBNP tests were measured in urban laboratories (72.7%) and in private (62.9%) non-hospital/clinics laboratories; they were mostly ordered by general practitioners (66% compared with 11% by cardiologists). The number of NT-proBNP measurements increased with age up to 80-90 years, and 70.3% of tests were measured in ≥75 years patients. Creatinine and electrolytes were not associated with NT-proBNP in 15.8% and 19.7% of tests, respectively. CONCLUSION: Among a very large cohort, we observed that natriuretic peptides remain largely undermeasured. NT-proBNP is mostly measured in elderly patients, and its interpretation may be hazardous in up to 16% of all individuals because no measurement of creatinine was associated to NT-proBNP.

Association between serum uric acid and left ventricular hypertrophy/left ventricular diastolic dysfunction in patients with chronic kidney disease.

BACKGROUND: The level of serum uric acid (SUA) has been reported to be associated with left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). However, this association remains unclear in patients with chronic kidney disease (CKD). METHODS: A total of 1025 patients with pre-dialysis CKD with preserved left ventricular systolic function were enrolled in this cross-sectional study. The LVH and LVDD were assessed using two-dimensional echocardiography and tissue Doppler imaging. The associations of LVH/LVDD with clinical and laboratory variables were investigated using univariable and multivariable logistic regression analyses. RESULTS: In a multivariable analysis, the SUA level was an independent predictor of LVH (odds ratio [OR]: 1.40, 95% confidence interval [CI]: 1.31-1.50, P < 0.001). In addition, patient age, systolic blood pressure, intact parathyroid hormone levels, and left atrial volume index levels were independent predictors of LVH. The SUA level was also an independent predictor of LVDD (OR: 1.93, 95% CI: 1.53-2.43, P < 0.001). Furthermore, systolic blood pressure and left atrial volume index levels were an independent predictor of LVDD. Receiver-operating characteristic curve analysis showed that the best cutoff values of SUA levels for identifying LVH and LVDD were ≥ 7.5 mg/dL and ≥ 6.3 mg/dL, respectively. CONCLUSION: The SUA level was an independent predictor of LVD and LVDD in patients with CKD, suggesting that SUA could be a biomarker for LVH and LVDD.

Elevated plasma fatty acid-binding protein 3 is related to prolonged corrected QT interval and reduced ejection fraction in patients with stable angina.

Background: Higher concentrations of plasma fatty acid-binding protein 3 (FABP3) play a role in the development of cardiovascular events, cerebrovascular deaths, and acute heart failure. However, little is known about the relationship between plasma FABP3 level and prolonged QT interval and reduced ejection fraction (EF). This study aimed to investigate the relationship between plasma FABP3 level and prolonged corrected QT (QTc) interval and reduced EF in patients with stable angina. Inflammatory cytokine and adipocytokine levels were also measured to investigate their associations with plasma FABP3. Methods: We evaluated 249 consecutive patients with stable angina. Circulating levels of FABP3 were measured by ELISA. In addition, 12-lead ECG and echocardiography recordings were obtained from each patient. Results: Multiple regression analysis showed that high-density lipoprotein cholesterol, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, visfatin, adiponectin, FABP4, heart rate, QTc interval, left atrial diameter, left ventricular mass index, end-systolic volume, end-systolic volume index, fractional shortening, and EF were independently associated with FABP3 (all p<0.05). Patients with an abnormal QTc interval had a higher median plasma FABP3 level than those with a borderline and normal QTc interval. With increasing FABP3 tertiles, the patients had higher frequencies of abnormal QTc interval, left ventricular systolic dysfunction, and all-cause mortality, incrementally lower EF, higher WBC count, and higher levels of hs-CRP, visfatin, adiponectin, and FABP4. Conclusion: This study indicates that plasma FABP3 may act as a surrogate parameter of prolonged QTc interval and reduced EF in patients with stable angina, partially through the effects of inflammation or cardiomyocyte injury. Further studies are required to elucidate whether plasma FABP3 plays a role in the pathogenesis of QTc prolongation and reduced EF.

Association of Pro-B-Type Natriuretic Peptide With Cardiac Magnetic Resonance-Measured Global and Regional Cardiac Function and Structure Over 10 Years: The MESA Study.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is widely used to diagnose and manage patients with heart failure. We aimed to investigate associations between NT-proBNP levels and development of global and regional myocardial impairment, dyssynchrony, and risk of developing myocardial scar over time. Methods and Results We included 2416 adults (45-84 years) without baseline clinical cardiovascular disease from MESA (Multi-Ethnic Study of Atherosclerosis). NT-proBNP was assessed at baseline (2000-2002). Cardiac magnetic resonance-measured left ventricular parameters were assessed at baseline and year 10 (2010-2012). Tagged cardiac magnetic resonance and myocardial dyssynchrony were assessed. We used linear and logistic regression models to study the relationships between quartiles of NT-proBNP levels and outcome variables. Left ventricular parameters decreased over time. After 10-year follow-up and adjusting for cardiovascular disease risk factors, people in the highest quartile had significantly greater decline in left ventricular ejection fraction (-1.60%; 95% CI, -2.26 to -0.94; P<0.01) and smaller decline in left ventricular end systolic volume index (-0.47 mL/m2; 95% CI, -1.18 to 0.23; P<0.01) compared with those in the lowest quartile. Individuals in the highest quartile had more severe risk factor adjusted global, mid, and apical regional dyssynchrony compared with those in the lowest, second, and third quartiles (all P-trend<0.05). Compared with the lowest-quartile group, the adjusted odds ratios for having myocardial scar was 1.3 (95% CI, 0.7-2.2) for quartile 2; 1.2 (95% CI, 0.6-2.3) for quartile 3; and 2.7 (95% CI, 1.4-5.5) for quartile 4 (P-trend=0.012) for the total sample. Conclusions Among participants without baseline clinical cardiovascular disease, higher baseline NT-proBNP concentration was significantly associated with subclinical changes in developing myocardial dysfunction, more severe cardiac dyssynchrony, and higher odds of having myocardial scar over a 10-year period independent of traditional cardiovascular disease risk factors.

Uric acid in chronic coronary syndromes: Relationship with coronary artery disease severity and left ventricular diastolic parameter.

BACKGROUND AND AIMS: Uric Acid (UA) has been related to the development of Cardio-Vascular (CV) events in patients affected by Chronic Coronary Syndromes (CCS). Among various hypothesis, two arise: UA may negatively act on coronary artery determining a higher degree of atherosclerotic disease, and/or on heart determining a higher prevalence of diastolic dysfunction. Both the above hypothesized effects are object of our investigation. METHODS AND RESULTS: 231 patients who were admitted to the cardiological department of the Niguarda Hospital (Milan, Italy) for CCS from January 2017 to June 2018 were enrolled. Coronary atherosclerotic burden was evaluated from coronary angiography as the number and type of involved vessels, as well as with both Gensini and Syntax scores. All subjects underwent a complete echocardiogram. At unadjusted and adjusted/multivariable analysis, UA levels were not significantly associated with variables analysed from the coronary angiography (number and type of vessels involved, neither the Gensini and Syntax scores) as well as with echocardiographic parameters regarding systolic and diastolic function. CONCLUSIONS: In conclusion, the main finding of our work is the absence of a role for UA in determining coronary arteries disease as well as LV diastolic dysfunction in CCS subjects. Taking together the results of previous studies with ours, we hypothesize that UA could act on heart (both on coronary arteries and on LV function) in an early phase of the disease, whereas while in the advanced stages other factors (previous myocardial infarction, previous myocardial revascularization and so on) may overshadow its effects.

Carvedilol and exercise combination therapy improves systolic but not diastolic function and reduces plasma osteopontin in Col4a3-/- Alport mice.

There are currently no Food and Drug Administration-approved treatments for heart failure with preserved ejection fraction (HFpEF). Here we compared the effects of exercise with and without α/ß-adrenergic blockade with carvedilol in Col4a3-/- Alport mice, a model of the phenogroup 3 subclass of HFpEF with underlying renal dysfunction. Alport mice were assigned to the following groups: no treatment control (n = 29), carvedilol (n = 11), voluntary exercise (n = 9), and combination carvedilol and exercise (n = 8). Cardiac function was assessed by echocardiography after 4-wk treatments. Running activity of Alport mice was similar to wild types at 1 mo of age but markedly reduced at 2 mo (1.3 ± 0.40 vs. 4.5 ± 1.02 km/day, P < 0.05). There was a nonsignificant trend for increased running activity at 2 mo by carvedilol in the combination treatment group. Combination treatments conferred increased body weight of Col4a3-/- mice (22.0 ± 1.18 vs. 17.8 ± 0.29 g in untreated mice, P < 0.01), suggesting improved physiology, and heart rates declined by similar increments in all carvedilol-treatment groups. The combination treatment improved systolic parameters; stroke volume (30.5 ± 1.99 vs. 17.8 ± 0.77 µL, P < 0.0001) as well as ejection fraction and global longitudinal strain compared with controls. Myocardial performance index was normalized by all interventions (P < 0.0001). Elevated osteopontin plasma levels in control Alport mice were significantly lowered only by combination treatment, and renal function of the Alport group assessed by urine albumin creatinine ratio was significantly improved by all treatments. The results support synergistic roles for exercise and carvedilol to augment cardiac systolic function of Alport mice with moderately improved renal functions but no change in diastole.NEW & NOTEWORTHY In an Alport mouse model of heart failure with preserved ejection fraction (HFpEF), exercise and carvedilol synergistically improved systolic function without affecting diastole. Carvedilol alone or in combination with exercise also improved kidney function. Molecular analyses indicate that the observed improvements in cardiorenal functions were mediated at least in part by effects on serum osteopontin and related inflammatory cytokine cascades. The work presents new potential therapeutic targets and approaches for HFpEF.

Echocardiographic Manifestations in COVID-19: A Review.

COVID-19 has rapidly spread around the world and threatened global health. Although this disease mainly affects the respiratory system, there is increasing evidence that SARS-CoV-2 also has effects on the cardiovascular system. Echocardiography is a valuable tool in the assessment of cardiovascular disease. It is cost-effective, widely available and provides information that can influence management. Given the risk of personnel infection and equipment contamination during echocardiography, leading world societies have recommended performing echocardiography only when a clinical benefit is likely, favouring focussed evaluations and using smaller portable equipment. In the past months, multiple reports have described a wide pattern of echocardiographic abnormalities in patients with COVID-19. This review summarises these findings and discusses the possible mechanisms involved.