Prognostic Implication of Liver Function Tests in Heart Failure With Preserved Ejection Fraction Without Chronic Hepatic Diseases: Insight From TOPCAT Trial.

Background: Liver dysfunction is prevalent in patients with heart failure (HF), but the prognostic significance of liver function tests (LFTs) remains controversial. Heart failure with preserved ejection fraction (HFpEF) had been introduced for some time, but no previous study had focused on LFTs in HFpEF. Thus, we aim to evaluate the prognostic significance of LFTs in well-defined HFpEF patients. Methods and Results: We conveyed a post-hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). The primary outcome was the composite of cardiovascular mortality, HF hospitalization, and aborted cardiac arrest, and the secondary outcomes were cardiovascular mortality and HF hospitalization. In Cox proportional hazards models, aspartate transaminase (AST) and alanine transaminase (ALT) were not associated with any of the outcomes. On the contrary, increases in total bilirubin (TBIL) and alkaline phosphatase (ALP) were associated with increased risks of the primary outcome [TBIL: adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI) 1.08-1.26; ALP: adjusted HR, 1.12; 95% CI 1.04-1.21], cardiovascular mortality (TBIL: adjusted HR, 1.16; 95% CI 1.02-1.31; ALP: adjusted HR, 1.16; 95% CI 1.05-1.28), and HF hospitalization (TBIL: adjusted HR, 1.22; 95% CI 1.12-1.33; ALP: adjusted HR, 1.12; 95% CI 1.03-1.23). Conclusion: Elevated serum cholestasis markers TBIL and ALP were significantly associated with a poor outcome in HFpEF patients without chronic hepatic diseases, while elevated ALT and AST were not.

Sex-Specific Associations of Risks and Cardiac Structure and Function With Microalbumin/Creatinine Ratio in Diastolic Heart Failure.

Background: Heart failure with preserved ejection fraction (HFpEF) affects women more frequently than men. However, data on sex-specific associations of adverse health outcomes and left ventricular structure and function and with microalbuminuria in patients with HFpEF are scarce. Methods: In 1,334 participants enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial, we estimated the sex-specific multivariable-adjusted risk and LV traits with urine microalbumin/creatine ratio (ACR), using Cox or linear regression. Results: In total, 604 (45.3%) were women. In multivariable-adjusted analyses, a doubling of ACR in both men and women was associated with higher posterior (+0.014 cm, p = 0.012/+0.012 cm, p = 0.033) wall thickness and left ventricular mass index (+2.55 mg/m2, p = 0.004/+2.45 mg/m2, p = 0.009), whereas was also associated with higher septal (+0.018 cm, p = 0.002) and left atrial volume index (+1.44 mL/m2, p = 0.001) in men. ACR was a key predictor of all-cause (HR, 1.11; p = 0.006) and cardiovascular (HR, 1.17; p = 0.002) death in women, whereas in men ACR was associated with HF hospitalization (HR, 1.23; p < 0.001), any hospitalization (HR, 1.06; p = 0.006), and myocardial infarction (HR, 1.19; p = 0.017). The interactions of sex with ACR were significant for hospitalization for heart failure and any hospitalization (p ≤ 0.034). Conclusions: Outcomes and cardiac structure and function in patients with HFpEF appear to be influenced by ACR that vary according to sex. In men, ACR was significant associated with LV diastolic function, hospitalization, and myocardial infarction, whereas in women was associated with mortality.

Associations of Left Ventricular Structure and Function With Blood Pressure in Heart Failure With Preserved Ejection Fraction: Analysis of the TOPCAT Trial.

Background Data on the association of systolic and diastolic blood pressure with the structure and function of failing hearts with preserved ejection fraction (EF) are sparse. Methods and Results This analysis included 935 patients with heart failure (49.4% women; mean age, 69.9 years) with preserved EF (≥45%) enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) Trial before initiation of randomized therapy. Left ventricular (LV) structure (dimensions, wall thickness, and mass index), diastolic function (left atrial volume index, transmitral blood flow, and mitral annular velocities), and systolic function (EF and longitudinal strain) were assessed echocardiographically. In multivariable-adjusted analyses, association sizes expressed per 1-SD (14.8-mm Hg) increment in systolic blood pressure were 0.020 cm (P=0.003) and 0.018 cm (P=0.004) for LV septal and posterior wall thickness, respectively, and 2.42 mg/m2 (P=0.018) for LV mass index. The corresponding associations with diastolic blood pressure were nonsignificant (P≥0.067). In similarly adjusted analyses, the association sizes expressed per 1-SD (10.7-mm Hg) increment in diastolic blood pressure were -0.15 for E/A (P<0.001), -0.76 for E/e' (P=0.006), and -0.62% for EF (P=0.024). These findings were consistent, if models including systolic blood pressure were additionally adjusted for diastolic blood pressure and vice versa, albeit that the relation of EF with diastolic blood pressure weakened (-0.54%; P=0.10). Conclusions In diastolic heart failure, LV wall thickness and LV mass index increased with higher systolic blood pressure, but not with higher diastolic blood pressure, whereas functional measures reflecting diastolic LV function decreased with higher diastolic blood pressure, independent of systolic blood pressure. These observations highlight the importance of controlling both systolic and diastolic blood pressure as modifiable risk factors to reduce the risk of LV remodeling and diastolic LV dysfunction.

Association of hyponatraemia and renal function in type 1 cardiorenal syndrome.

BACKGROUND: Hyponatraemia predicts type 1 cardiorenal syndrome in acute decompensated heart failure patients, which associates with poor outcome. Recovery from hyponatraemia has been found to associate with better outcome in acute decompensated heart failure patients, but its prognostic value regarding renal function remains unknown. METHODS: We performed a secondary analysis of CARRESS-HF trial, and all patients included had worsening renal function (≥0.3 mg/dL increase in serum creatinine than the nadir). The serum sodium levels of patients were evaluated at baseline and day 4 and day 7 after randomization. Patients were grouped according to the status of hyponatraemia: recovery from hyponatraemia; no hyponatraemia; persistent hyponatraemia; and new-onset hyponatraemia. Their associations with persistent worsening renal function (serum creatinine ≥ 0.3 mg/dL higher than the nadir at discharge) were explored. RESULTS: A total of 118 patients suffered from persistent worsening renal function. Baseline hyponatraemia was not associated with persistent worsening renal function (odds ratio = 0.495, P = .086). Patients in the recovery from hyponatraemia group had a lowest risk of persistent worsening renal function among the study population. Further, baseline serum sodium level was not associated with the risk of persistent worsening renal function (odds ratio = 1.055, P = .233), while the increases in serum sodium level at day 4 (odds ratio = 0.858, P = .003) and at day 7 (odds ratio = 0.821, P < .001) significantly predicted a lower risk of persistent worsening renal function. CONCLUSIONS: Recovery from hyponatraemia associates with a lower risk of persistent worsening renal function, suggesting that hyponatraemia correction may improve renal outcomes in acute decompensated heart failure patients with type 1 cardiorenal syndrome.

Association between retinal arterial narrowing and left ventricular diastolic dysfunction in masked hypertensives.

Morphological change in retinal vessel diameters has been reported to be associated with negative cardiovascular outcomes, but its association with left ventricular diastolic dysfunction (LVDD) is not clear. This study aimed to examine the association between echocardiographic markers of LVDD and retinal vascular diameters, in untreated masked hypertension (MH). In this observational study, 105 MH patients without other cardiovascular risks were included (mean age 48.4 ± 5.7, female 72.4%). All individuals underwent extensive clinical and laboratory investigations, including echocardiography, ambulatory blood pressure monitoring, and retinal vascular diameters measured by optical coherence tomography. In the group, LVDD was diagnosed in 36 participants evaluated by left ventricular volume index, E/A and E/e' ratio. Compared to non-LVDD, LVDD subjects displayed narrower retinal arteriolar diameter (139.1 ± 33.8 vs 165.1 ± 29.1; adjusted P = .007) and wider retinal venular diameter (237.9 ± 42.2 vs 214.9 ± 44.8; adjusted P = .045). Significant and independent associations were demonstrated for retinal arteriolar narrowing and E/A ratio (adjusted ß = 0.744, P = .031) and for retinal arteriolar diameter and E/e' ratio (adjusted ß = -0.158, P = .001) after controlling for age, gender, body mass index, ambulatory systolic blood pressure, low-density lipoprotein cholesterol, and retinal venular diameter. In untreated MH subjects, retinal arteriolar diameter, a marker of microvascular damage, was independently associated with echocardiographic markers of diastolic dysfunction. These findings might underscore the hypothesis that microvascular disease could contribute to cardiac remodeling.

Mean platelet volume/platelet count ratio predicts long-term mortality in patients with infective endocarditis.

Aim: We aimed to examine the association between baseline mean platelet volume/platelet count ratio (MPR) and all-cause mortality in patients with infective endocarditis (IE). Patients & methods: This study analyzed 218 consecutive patients with IE and divided them into four groups based on MPR quartiles. We used Kaplan-Meier survival curves to determine the cumulative survival and Cox proportional hazards models to investigate the association between MPR and all-cause mortality after hospital discharge. Results: Kaplan-Meier curves showed a gradual increase in mortality risk from the lowest MPR quartile to the highest quartile. Multivariate analysis revealed that MPR was an independent predictor of increased risk for all-cause death. Conclusion: Elevated MPR was independently associated with long-term all-cause mortality in patients with IE.

Prognostic Value of Cysteine-Rich Protein 61 Combined with N-Terminal Pro-B-Type Natriuretic Peptide for Mortality in Acute Heart Failure Patients with and without Chronic Kidney Disease.

BACKGROUND: The ability of most biomarkers, such as N-terminal pro-B-type natriuretic peptide (NT-proBNP), to predict prognosis in heart failure can be affected by the state of renal function; therefore, there is the need for a biomarker that can predict prognosis accurately without the influence of renal function. The prognostic value of cysteine-rich protein 61 (CYR61/CCN1) in acute heart failure (AHF) patients has been proven. METHODS: A total of 248 patients hospitalized with AHF were recruited in this study, and serum CCN1 levels, NT-proBNP levels, and other necessary data of patients were collected upon admission. The correlation of serum CCN1 with estimated glomerular filtration rate (eGFR) was investigated, and the logistic regression model was used to investigate the prognostic value of serum CCN1 for 3-month mortality. RESULTS: Fifty-four of 248 patients died (21.8%) during a 3-month follow-up. Serum CCN1 had no significant correlation with eGFR (rho = -0.088, p = 0.167). In the overall population and patients without chronic kidney disease, results showed that both serum CCN1 and NT-proBNP were significantly associated with 3-month mortality. In patients with chronic kidney disease, serum CCN1 was significantly associated with 3-month mortality in logistic regression analysis (odds ratio = 2.40, p = 0.002) while NT-proBNP was not. Further in tertile group comparison, in patients with chronic kidney disease, higher tertile levels of serum CCN1 had a significantly higher risk of 3-month mortality compared to the lower tertile ones (odds ratio = 4.17, p = 0.013), but that of NT-proBNP did not. CONCLUSION: Serum CCN1 level is not associated with eGFR, and it maintains the prognostic value in AHF patients with chronic kidney disease. CCN1 could be a potential novel prognostic biomarker in AHF patients with chronic kidney disease.