The Value of Echocardiography Combined with NT-pro BNP Level in Assessment and Prognosis of Diastolic Heart Failure.

BACKGROUND: To investigate the significance of echocardiography combined with N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels in the evaluation and prognosis of diastolic heart failure (DHF). METHODS: Clinical data were collected from 168 patients with DHF. Serum levels of NT-pro BNP were first measured by ELISA. Meanwhile, the echocardiography was used to examine left ventricular end-diastolic diameter (LVEDD), left ventricular diameter (LVD), and other parameters. Multivariate logistic regression analysis was performed for variables in heart failure assessment grade or poor prognosis. Finally, the predictive ability for New York Heart Association (NYHA) class as well as prognosis was assessed by ROC curves. RESULTS: NT-pro BNP was the overexpression in the serum of patients with DHF. And the degree of elevation was related to NYHA class, while NT-pro BNP levels were significantly higher in the P-MACE group than in the N-MACE group. According to the multivariate logistic regression analysis, the ratio of peak velocity of left atrial early diastolic blood flow to early diastolic peak velocity of mitral annulus (E/Ea) and serum NT-pro BNP level was risk factors for NYHA class and prognosis. However, LVEF, LVEDD, and flow propagation velocity (Vp) can be a benefit condition. In addition, ROC curve showed that echocardiography combined with NT-pro BNP content had higher accuracy in NYHA class and prognostic assessment of DHF than applied separately. CONCLUSIONS: The diagnosis of echocardiography combined with NT-pro BNP levels has the potential to distinguish the NYHA class in heart function of patients with DHF and determine the prognosis of patients.

Prognostic relevance of elevated plasma osmolality on admission in acute decompensated heart failure with preserved ejection fraction: insights from PURSUIT-HFpEF registry.

BACKGROUND: Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. METHODS: We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan-Meier curve analysis and Cox proportional hazard testing. RESULTS: 216 (22.5%) patients reached the primary endpoint. Kaplan-Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25-23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46-21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e', and N-terminal pro-B-type natriuretic peptide elevation. CONCLUSIONS: Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

Improvement of Shen'ge formula on heart function in diastolic heart failure: A protocol for randomized, double-blind, placebo-controlled clinical study.

INTRODUCTION: Diastolic heart failure (DHF) is an important pathological type of heart failure, that involves multiple organ dysfunction and multiple complications. The prevalence of DHF is high, and effective treatments are lacking. Chinese herbs are an alternative therapy for DHF. Shen'ge formula (SGF) is a classical formula from which patients can benefit, but convincing evidence of its efficacy is lacking. Therefore, we designed this randomized controlled trial protocol. METHODS/DESIGN: This randomized, double-blind, placebo-controlled clinical trial will evaluate the efficacy and safety of SGF in the treatment of DHF. A total of 130 patients with DHF will be enrolled in the trial and treated with SGF granules or placebo for 12 weeks and followed up for 12 weeks. The primary outcome measurement will be to changes in plasma N-terminal brain natriuretic peptide precursor before versus after treatment, while the second primary outcome measurement will be changes in heart function before versus after treatment and the 12-week follow-up period. It will also include echocardiography, a cardiopulmonary exercise test, cardiac function grading, traditional Chinese medicine syndrome score, and the Minnesota Heart Failure Quality of Life Scale. Adverse events will be evaluated throughout the trial. DISCUSSION: The results of this trial will demonstrate whether SGF could alleviate symptoms, improve cardiac function, reduce readmission rates, and improve quality of life of patients with DHF. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2000036533, registered on August 24, 2020.

Use of Inflammatory Biomarkers and Real-Time Cardiac Catheterisation to Evaluate the Left Ventricular Diastolic Function in Patients With Diastolic Heart Failure.

BACKGROUND: Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF). METHODS: A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography. The follow-up period was 30 (18, 35) months. RESULTS: The levels of IL-17 and IL-6 from the systemic blood were significantly increased in non-heart failure (HF) patients with LVDD (p<0.001). Receiver operating characteristic (ROC) revealed that the combination of IL-17 and IL-6 showed the highest diagnostic accuracy in predicting LVDD (AUC, 0.890; 95% CI, 0.835-0.945; p<0.001), and the cut-off value was 41.5 pg/mL. On logistic regression analysis, the increment of the combination of IL-17 and IL-6 was an independent predictor for the prognosis of LVDD (odds ratio, 1.25; 95% CI, 1.01-1.12; p<0.05). According to the cut-off value of the combination of IL-17 and IL-6, the patients with lower levels of IL-17 and IL-6 (<41.5 pg/mL group) had a better prognosis. The increased levels of IL17 and IL-6 were significantly correlated with the levels of fibrotic parameters. CONCLUSIONS: Assessment of LVDD by measuring the combination of IL-17 and IL-6 might provide valuable prognostic significance for non-HF patients with LVDD.

Lipid Biomarkers as Predictors of Diastolic Dysfunction in Diabetes with Poor Glycemic Control.

Uncontrolled type-1 diabetes (T1DM) can lead to dyslipidaemia and albuminuria, which may promote cardiovascular injuries. However, some lipidemic factors could be useful in predicting cardiac dysfunction. Seventy-eight adolescents under insulin treatment due to a 6-year history of T1DM and were retrospectively examined. Glycemia, lipidemia, and albuminuria were measured in addition to development of cardiovascular abnormalities Both girls and boys showed higher HbA1c and fasting blood glucose and 27.1% females and 33.3% males exhibited microalbuminuria though their plasma levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL) and high-density lipoproteins (HDL lipoproteins were in the normal range. They exhibited a preserved systolic function, but 50% of females and 66.6% of males had developed diastolic failures. Interestingly, girls with diastolic dysfunction showed significantly lower concentrations of HDL and higher TC/HDL and TG/HDL ratios. In fact, low HDL levels (OR 0.93; 95% CI 0.88-0.99; p = 0.029) and high TC/HDL (OR 2.55; 95% CI 1.9-5.45; p = 0.016) and TG/HDL (OR 2.74; 95% CI 1.12-6.71; p = 0.028) ratios associated with the development of diastolic complications. The cut-off values for HDL, TC/HDL, and TG/HDL were 49 mg/dL, 3.0 and 1.85, respectively. HDL and TC/HDL and TG/HDL ratios may be useful for predicting diastolic dysfunction in girls with uncontrolled T1DM.

Circulating Connective Tissue Growth Factor Is Associated with Diastolic Dysfunction in Patients with Diastolic Heart Failure.

BACKGROUND: Connective tissue growth factor (CTGF) and transforming growth factor ß1 (TGF-ß1) are emerging biomarkers for tissue fibrosis. The aim of this study was to investigate the association between circulating CTGF, TGF-ß1 levels and cardiac diastolic dysfunction in patients with diastolic heart failure (DHF). METHODS: Admitted subjects were screened for heart failure and those with left ventricular (LV) ejection fraction <45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Totally 114 patients with DHF and 72 controls were enrolled. Plasma levels of CTGF, TGF-ß1, and B-type natriuretic peptide (BNP) were determined. RESULTS: The plasma CTGF and TGF-ß1 levels increased significantly in patients with DHF. Circulating CTGF and TGF-ß1 levels were correlated with echocardiographic parameter E/e' and diastolic dysfunction grading in DHF patients. In multivariate logistic analysis, CTGF was significantly associated with diastolic dysfunction (odds ratio: 1.027, p < 0.001). Plasma CTGF (AUC: 0.770 ± 0.036, p < 0.001) and CTGF/BNP (AUC: 0.839 ± 0.036, p < 0.001) showed good predictive power to the diagnosis of DHF. CONCLUSIONS: This finding suggested CTGF could be involved in the pathophysiology of diastolic heart failure and CTGF/BNP might have auxiliary diagnostic value on diastolic heart failure.

The effect of perindopril on echocardiographic parameters, NYHA functional class and serum NT-proBNP values in patients with diastolic heart failure.

INTRODUCTION: Growing evidence has demonstrated that diastolic heart failure occurs in about half of heart failure (HF) patients. We investigated the effects of perindopril on echocardiographic parameters, New York Heart Association (NYHA) functional class and serum N-terminal pro B-type natriuretic peptide (NT-proBNP) levels in patients with diastolic heart failure. METHODS: In total, 108 diastolic heart failure patients aged ≥ 50 years, who had diastolic dysfunction with an ejection fraction ≥ 50%, were enrolled and randomised to one of the two study groups. Perindopril was initiated in the study group and the control group was given standard therapy. Echocardiographic parameters, NT-proBNP levels and NYHA classes were recorded. The patients were followed for 11 (three to 16) months. Eighty-eight patients completed the study. RESULTS: Although diastolic parameters were not changed, A' (septal) velocity (10.8 vs 9.9 cm/s) and Sm (septal) velocity (8.5 vs 7.6 cm/s) were significantly increased in the perindopril compared to the control group. A significant increase in A' (septal) velocity (+0.61 vs -0.28 cm/s, p = 0.04) and a slight increase in Sm (septal) velocity (+0.99 vs 0.36 cm/s, p = 0.054) were noted in the perindopril group. CONCLUSIONS: Tissue Doppler septal late diastolic velocities and septal systolic myocardial velocities increased in the perindopril group but NT-proBNP levels, and NYHA class was not changed in this study population.

Circulating Activin A Is a Surrogate for the Incidence of Diastolic Dysfunction and Heart Failure in Patients With Preserved Ejection Fraction.

BACKGROUND: Diastolic dysfunction (DD) is a characteristic of heart failure with preserved ejection fraction (HFpEF), which is thought to be caused by cardiac hypertrophy or fibrosis. Activin A is involved in the inflammatory response and myocardial fibrosis, but the relationship between the activin A level and DD remains unclear.Methods and Results:A total of 209 patients with stable angina were enrolled. Serum activin A levels were assessed, and echocardiography and cross-sectional analysis were performed. Among the subjects (65% male; mean age, 70±13 years), 84 (40%) subjects had DD. The subjects were divided into tertiles based on activin A levels. Patients in the high activin A group had enhanced left ventricular mass indexes, medial E/e' ratios, left atrial diameter, and right ventricular systolic pressure compared with those in the lower activin A groups (all P<0.001). Prevalence of DD (P=0.001), HFpEF at enrollment (P=0.007), and the composite endpoints including new-onset heart failure (HF) or death within 3 years (P<0.001) correlated positively with high activin A levels. After adjusting for confounding factors, high activin A levels remained significantly associated with DD (P=0.036) and the composite endpoints (P=0.012). CONCLUSIONS: Enhanced serum activin A levels were associated with the incidence of DD and development of HF.

Comparison of Prognostic Usefulness of Serum Insulin-Like Growth Factor-Binding Protein 7 in Patients With Heart Failure and Preserved Versus Reduced Left Ventricular Ejection Fraction.

We aimed to characterize of the role of insulin-like growth factor-binding protein 7 (IGFBP-7) in heart failure (HF) pathophysiology. IGFBP-7 has been associated with cardiac hypertrophy and diastolic dysfunction in HF. In 86 patients with HF with a preserved ejection fraction (HFpEF) (ejection fraction [EF] ≥45%) and 79 with HF with a reduced ejection fraction (HFrEF), we assessed concentrations of serum IGFBP-7, correlations between serum IGFBP-7 and clinical data, diastolic function, and associations with outcome. IGFBP-7 was lower in HFpEF than HFrEF (102 vs 152 µg/L, p <0.001) and correlated with New York Heart Association class (HFpEF: r = 0.25, p = 0.020; HFrEF: r = 0.26, p = 0.022), N-terminal pro-brain natriuretic peptide (NT-proBNP) (HFpEF: r = 0.53, p <0.001; HFrEF: r = 0.50, p <0.001), and estimated glomerular filtration rate (eGFR) (HFpEF: r = -0.47, p <0.001; HFrEF: r = -0.45, p <0.001). In HFpEF, IGFBP-7 correlated with E/e' (r = 0.31, p = 0.012) and E/A ratio (r = 0.31, p = 0.011). In HFrEF, but not HFpEF, IGFBP-7 correlated with age (r = 0.29, p = 0.009) and atrial fibrillation (r = 0.34, p = 0.002). IGFBP-7 predicted the outcome in HFpEF (hazard ratio 4.19 [1.01 to 17.35], p = 0.048]) but not in HFrEF (0.72 [0.24 to 2.14], p = 0.554). In conclusion in HFrEF, IGFBP-7 was elevated and associated with HF severity but not prognostic, suggesting a marker of risk. In HFpEF, IGFBP-7 was less elevated but associated with markers of diastolic dysfunction, HF severity, and prognosis. IGFBP-7 may contribute to the progression of HFpEF possibly through inflammation and oxidative stress.

Complexity of pathomechanisms leading to diastolic heart failure in diabetes mellitus - potential field for therapeutic interventions?

Advanced glycation end products (AGE) have been implicated in diabetes associated complications. They have been suggested as potential mediators in the progression of diabetic heart failure and as a potential target for treatment. Brunvand et al. now provided evidence in that the suggested causal relationship between AGE and diastolic myocardial dysfunction cannot be confirmed in children with type 1 diabetes. The early signs of diastolic myocardial impairment were associated with higher BMI, but not with HbA1c levels. Furthermore, higher serum levels of MG-H1 and increased arterial stiffness were not significantly associated with diastolic dysfunction. The lack of association argues against an essential role of AGEs. This sobering finding does not support the potential to treat diastolic dysfunction by reduction approaches AGE in type 1 diabetic patients. Further pathogenic mechanisms involved in diabetic cardiomyopathy, such as alterations of calcium metabolism, or remodeling of the extracellular matrix, and intramyocardial inflammation may be further promising therapeutic targets.

Low adiponectin is associated with diastolic dysfunction in women: a cross-sectional study from the Tromsø Study.

BACKGROUND: Heart failure with preserved ejection fraction is closely associated with diastolic dysfunction and related to obesity and female sex. We investigated whether adiponectin, an adipocyte-secreted protein hormone with cardioprotective effects, was associated with indices of diastolic dysfunction, and whether the association was sex dependent. METHODS: We conducted a cross-sectional study on 1165 women and 896 men without diabetes. We stratified the multivariable adjusted logistic regression analyses and the fractional polynomial regression analyses according to sex, with echocardiographic markers of diastolic dysfunction as dependent variables, and adiponectin as the independent variable of interest. RESULTS: Decreased adiponectin was associated with higher odds of average tissue Doppler e' < 9 in women (odds ratio [OR] 1.17 per 1 µg/mL adiponectin decrease, 95% confidence interval [CI] 1.04-1.30), but not in men (p for interaction with sex 0.04). Women, but not men, had higher odds of E/e' ratio ≥ 8 with lower adiponectin (OR 1.12 per 1 µg/mL adiponectin decrease, 95% CI 1.02-1.24, p for interaction with sex 0.04). Adiponectin in the lower sex-specific tertile was associated with increased odds of concentric left ventricular hypertrophy in women (OR 2.44, 95% CI 1.03-5.77), but with decreased odds in men (OR 0.32, 95% CI 0.11-0.88, p for interaction with sex 0.002), and decreased odds of eccentric hypertrophy in men only (OR 0.53, 95% CI 0.33-0.88, p for interaction with sex 0.02). Adiponectin in the lower sex-specific tertile was associated with moderately enlarged left atria in women only (OR 1.43, 95% CI 1.01-2.03, p for interaction with sex 0.04). Finally, adiponectin had a non-linear relationship with left ventricular mass in women only, with exponentially increasing left ventricular mass with lower adiponectin levels (p for interaction with sex 0.01). CONCLUSIONS: Low adiponectin was associated with higher odds of indices of diastolic dysfunction in women, but lower odds of indices of diastolic dysfunction in men. Lower adiponectin was associated with increased left ventricular mass in women only.

Insulin-Like Growth Factor-Binding Protein-7 as a Biomarker of Diastolic Dysfunction and Functional Capacity in Heart Failure With Preserved Ejection Fraction: Results From the RELAX Trial.

OBJECTIVES: This study sought to investigate relationships between insulin-like growth factor-binding protein-7 (IGFBP7) and parameters of diastolic function or functional capacity in patients with heart failure and preserved ejection fraction (HFpEF) who were randomized to receive sildenafil or placebo. BACKGROUND: IGFBP7 was previously found to be associated with diastolic function in heart failure with reduced ejection fraction, but it is unclear whether these associations are present in HFpEF. METHODS: At baseline and 24 weeks, IGFBP7, imaging studies, and peak oxygen consumption (Vo2max) were obtained and compared in 160 patients with HFpEF who were randomized to receive sildenafil or placebo. RESULTS: Patients with supramedian baseline IGFBP7 concentrations were older, had signs of systemic congestion and worse renal function, and had higher concentrations of prognostic heart failure biomarkers including amino-terminal pro-B-type natriuretic peptide (p < 0.05). Higher baseline IGFBP7 was modestly correlated with worse diastolic function: higher E velocity (Spearman correlation [ρ] = 0.40), E/E' (ρ = 0.40), left atrial volume index (ρ = 0.39), and estimated right ventricular systolic pressure (ρ = 0.41; all p < 0.001) and weakly correlated with transmitral E/A (ρ = 0.26; p = 0.006). Notably, change in IGFBP7 was significantly correlated with change in E, E/A, E/E', and right ventricular systolic pressure. Elevated baseline IGFBP7 was associated with lower baseline Vo2max (13.2 vs. 11.1 ml/min/kg; p < 0.001), and change in IGFBP7 was weakly inversely correlated with change in Vo2max (ρ = -0.19; p = 0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 24 weeks, in contrast to placebo-treated patients (median change in IGFBP7 -1.5 vs. +13.6 ng/ml; p < 0.001). CONCLUSIONS: In patients with HFpEF, IGFBP7 may be a novel biomarker of diastolic function and exercise capacity.

Circulating Fibroblast Growth Factor 21 is Associated with Diastolic Dysfunction in Heart Failure Patients with Preserved Ejection Fraction.

Fibroblast growth factor 21 (FGF21), a polypeptide ligand promoted glucose homeostasis and lipids metabolism, was recently reported to attenuate cardiac hypertrophy. The aim of this study was to investigate the impact of FGF21 in diastolic heart failure. Subjects admitted for coronary angiogram were screened for heart failure, and those with left ventricular (LV) ejection fraction < 45% were excluded. Diastolic dysfunction was defined as functional abnormalities that exist during LV relaxation and filling by echocardiographic criteria. Plasma levels of FGF21 and N-terminal Pro-Brain Natriuretic Peptide (NT-pro-BNP) were determined. All patients were followed up for 1 year, or till the occurrence of heart failure readmission or death. Totally 95 patients with diastolic dysfunction and 143 controls were enrolled. Circulating FGF21 level was correlated with echocardiographic parameters of diastolic function and LV end-diastolic pressure (LVEDP). In multivariate logistic analysis, FGF21 was significantly associated with diastolic dysfunction, either identified by echocardiographic criteria (odds ratio: 2.97, p = 0.012) or confirmed with LVEDP level (odds ratio: 3.73, p = 0.030). Both plasma FGF21 (log rank p < 0.0001) and NT-pro-BNP levels (log rank p = 0.0057) showed good predictive power to the 1-year adverse cardiac events. This finding suggested FGF21 could be involved in the pathophysiology of diastolic heart failure.

Risks and predictors of mild diastolic dysfunction among middle-aged and aged women: a population-based cohort study.

We sought to determine the predictors of primary episodes of mild diastolic dysfunction (DD) in a cohort of women aged >45 years, who had >2 echocardiography from 2009 to 2012. Patients were excluded if they had prior diagnosis of coronary artery disease, heart failure, valvular heart disease or echocardiographic evidence of DD. Mild DD was defined as: left ventricular ejection fraction>50%, E/A ratio<0.75, and E/e'⩽8. Out of the total 758 subjects (age 64.15±7.24 years), 109 (14.3%) had developed mild DD, during a mean followup period of 3 years. Independent predictors of mild DD included: age (P<0.001), history of hypertension (P=0.022), body mass index (BMI) (P<0.001), total triglycerides (TG) (P=0.016), inter ventricular septal thickness (P=0.015) and brachial-ankle pulse wave velocity (baPWV) ⩾16 m s(-1) (P<0.001). E/A ratio was inversely associated with age (r=-0.337, P<0.001), baPWV (r=-0.359, P<0.001), BMI (r=-0.290, P<0.001) and TG (r=-0.255, P<0.001). The Area Under roc Curve for a linear combination of age, BMI, baPWV and TG was 0.738 (95% confidence interval: 0.683-0.804, P<0.001), which was superior to any of the variables taken alone. In summary, many middle-aged or elderly women may develop mild DD within a relatively short period of 3 years. Several subclinical abnormalities and cardiovascular parameters were determined to contribute to the onset of DD.

Altered Metabolic Profile With Sodium-Restricted Dietary Approaches to Stop Hypertension Diet in Hypertensive Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a distinct entity with unique pathophysiology. In the Dietary Approaches to Stop Hypertension in Diastolic Heart Failure (DASH-DHF) study, the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) was associated with improved blood pressure and cardiovascular function in 13 hypertensive patients with HFpEF. With the use of targeted metabolomics, we explored metabolite changes and their relationship with energy-dependent measures of cardiac function in DASH-DHF. METHODS AND RESULTS: With the use of chromatography and mass spectrometry, 152 metabolites including amino acids, free fatty acids, phospholipids, diglycerides, triglycerides, cholesterol esters, and acyl carnitines were measured. Comparison of baseline and post-DASH/SRD samples revealed increases in short-chain acetyl, butryl, and propionyl carnitines (P values .02, .03, .03, respectively). Increases in propionyl carnitine correlated with ventricular-arterial coupling ratio (Ees:Ea; r = 0.78; P = .005) and ventricular contractility (maximum rate of change of pressure-normalized stress [dσ*/dtmax]; r = 0.66; P = .03). Changes in L-carnitine also correlated with Ees:Ea (r = 0.62; P = .04) and dσ*/dtmax (r = 0.60; P = .05) and inversely with ventricular stiffness (r = -0.63; P = .03). CONCLUSIONS: Metabolite profile changes of patients with HFpEF during dietary modification with the use of DASH/SRD suggest improved energy substrate utilization. Additional studies are needed to clarify connections between diet, metabolic changes, and myocardial function in HFpEF.

Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals.

OBJECTIVES: This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality. BACKGROUND: HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information. METHODS: Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction <50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index. RESULTS: Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy. CONCLUSIONS: Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.

[GDF-15, MRproADM, CTproET1, and CTproAVP in patients with asymptomatic diastolic dysfunction]. / GDF-15, MRproADM, CTproET1 und CTproAVP bei Patienten mit asymptomatischer diastolischer Dysfunktion.

BACKGROUND: The role of biomarkers in asymptomatic diastolic dysfunction (DD) has not been investigated so far. The aim of the study was to evaluate the clinical associations and the diagnostic property of different biomarkers in patients with asymptomatic DD. METHODS: Within a population based observational study, healthy participants (50-85 years) with an LVEF ≥ 50 % and no cardiovascular risk factor were prospectively identified. Patients were classified as having either DD (grade ≥ 1, n = 103) or no DD (CON: n = 85). All patients underwent physical examination including medical history, six-minute-walk-testing, QoL (SF-36), comprehensive echocardiography and blood sampling to measure routine values and specified biomarkers (NTproBNP, MRproANP, GDF-15, MRproADM, CTproET1, CTproAVP). RESULTS: In the DD-group plasma concentration of GDF-15 (p = 0,002), MRproADM (p < 0,001), and CTproAVP (p = 0,003) were significantly higher than in the CON-group. In contrast, NTproBNP (p = 0,390), MRproANP (p = 287), and CTproET1 (p = 0,393) did not differ. GDF-15, MRproADM and CTproAVP were significantly associated with the presence of DD. However, the significance of the seen associations was lost after multiple adjustments. NTproBNP, MRproANP, and MRproADM were significantly related to E / e' as a continuous measure of diastolic function. The significance of the seen associations was lost after multiple adjustments. In ROC analyses, none of the investigated biomarkers was able to relevantly improve the diagnosis of DD. CONCLUSION: In patients with asymptomatic DD plasma concentrations of GDF-15, MRproADM and CT-proAVP were significantly higher when compared with controls. In contrast, NTproBNP, MRproANP and CTproET1 did not differ. After adjustment for age, sex, BMI and renal function, no significant association between DD or E / e' and different biomarkers could be observed. Furthermore, none of the investigated biomarkers was able to substantially improve the diagnosis of DD.

Worsening diastolic function is associated with elevated fasting plasma glucose and increased left ventricular mass in a supra-additive fashion in an elderly, healthy, Swedish population.

AIMS: To examine whether increasing fasting plasma glucose (FPG) levels were associated with worsening left ventricular (LV) diastolic function, independently of LV mass index (LVMI) in elderly, otherwise healthy subjects. METHODS AND RESULTS: We tested cross-sectional associations between echocardiographically determined averaged E/é ratio/diastolic function, LVMI, cardiovascular risk factors, and FPG categorized as normal (NFG), impaired (IFG), and new-onset diabetes mellitus (DM), in 483 men and 208 women aged 56-79 years without overt cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid-lowering drugs and had a preserved LV ejection fraction >50%. Median E/é was significantly higher among subjects with diabetes than those without (8 vs. 7; p = 0.03), as was the prevalence of grade 2 or 3 diastolic dysfunction (25% vs. 16%; p = 0.02). E/é and diastolic function were significantly associated with LVMI (p ≤ 0.002), but not FPG category, on multivariable analysis. However, interaction analyses revealed that increasing LVMI was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG > 6 mmol/L (ß=0.005 for IFG and DM vs. 0.001 for NFG; p = 0.02), whereas increasing systolic blood pressure was primarily associated with worsening diastolic function (higher E/é) in subjects with FPG ≤ 6.9 mmol/L (ß = 0.005 for NFG and 0.003 for IFG vs. -0.001 for DM; p=0.001). CONCLUSION: Diastolic dysfunction was significantly more prevalent among patients with DM than those without. The importance of LVMI increased, but the importance of systolic blood pressure decreased with higher FPG category.

Galectin-3 in heart failure with preserved ejection fraction. A RELAX trial substudy (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure).

OBJECTIVES: This study hypothesized that elevated galectin-3 (Gal-3) levels would identify patients with more advanced heart failure (HF) with preserved ejection fraction (HFpEF) as assessed by key pathophysiological domains. BACKGROUND: Gal-3 is implicated in the pathogenesis of cardiac fibrosis but is also increased with normal aging and renal dysfunction. Cardiac fibrosis may contribute to cardiac dysfunction, exercise intolerance, and congestion in HFpEF. METHODS: Two hundred eight patients from the RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure) trial of sildenafil in HFpEF had Gal-3 measured at enrollment. Pathophysiological domains assessed included biomarkers of neurohumoral activation, fibrosis, inflammation and myocardial necrosis, congestion severity and quality of life, cardiac structure and function, and exercise performance. Analysis adjusted for age, sex, and/or cystatin-C levels. Potential interaction between baseline Gal-3 and treatment (sildenafil) effect on the RELAX study primary endpoint (change in peak oxygen consumption) was tested. RESULTS: Gal-3 levels were associated with age and severity of renal dysfunction. Adjusting for age, sex, and/or cystatin-C, Gal-3 was not associated with biomarkers of neurohumoral activation, fibrosis, inflammation or myocardial necrosis, congestion or quality-of-life impairment, cardiac remodeling or dysfunction, or exercise intolerance. Gal-3 did not identify patients who responded to phosphodiesterase type 5 (PDE-5) inhibitors (interaction p = 0.53). CONCLUSIONS: In overt HFpEF, Gal-3 was related to severity of renal dysfunction and accounting for this, was not independently associated with severity of pathophysiological derangements or response PDE-5 inhibition. These findings underscore the need to adjust for renal function when interpreting Gal-3 levels, and call into question the value of Gal-3 to quantify disease severity in overt HFpEF.