The Special Issue "Metabolic Regulation in the Development of Cardiovascular Disease and Heart Failure" focused on how metabolic diseases could cause a predisposition to cardiovascular diseases and, ...in particular, heart failure due to systolic or diastolic dysfunction or a combination thereof ....
Circulating microRNAs (miRs) are promising biomarkers for heart failure (HF). Previous studies have provided inconsistent miR "signatures." The phenotypic and pathophysiologic heterogeneity of HF may ...have contributed to this inconsistency. In this study we assessed whether advanced HF (AHF) patients present a distinct miR signature compared with healthy subjects (HS) and mild to moderate HF (MHF) patients.
The study consisted of 2 phases: a screening phase and a validation phase. In the screening phase, 752 miRs were profiled in HS and MHF and AHF patients (N = 15), using the real-time quantitative polymerase chain reaction (RT-qPCR) technique and global mean normalization. In the validation phase, the miRs found to be significantly dysregulated in AHF patients compared with both HS and MHF patients were validated in 15 HS, 25 patients with MHF and 29 with AHF, using RT-qPCR, and normalizing to exogenous (cel-miR-39) and endogenous controls.
In the screening phase, 5 miRs were found to be significantly dysregulated: -26a-5p; -145-3p; -150-5p; -485-3p; and -487b-3p. In the validation phase, miR-150-5p was confirmed to be significantly downregulated in AHF patients when compared with both HS and MHF patients, irrespective of the normalization method used. miR-26a-5p was confirmed to be significantly dysregulated only when normalized to cell-miR-39. Dysregulation of the other miRs could not be confirmed. miR-150-5p was significantly associated with maladaptive remodeling, disease severity and outcome.
Our data suggest miR-150-5p as a novel circulating biomarker for AHF. The association of miR-150-5p with maladaptive remodeling, disease severity and outcome supports the pathophysiologic relevance of downregulated miR-150-5p expression to AHF.
The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that ...renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium-glucose cotransporters sodium-glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin-angiotensin-aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective.
Chronic heart failure (CHF) leads to an excess of urgent ambulatory visits, recurrent hospital admissions, morbidity, and mortality regardless of medical and non-medical management of the disease. ...This excess of risk may be attributable, at least in part, to comorbid conditions influencing the development and progression of CHF. In this perspective, the authors examined and described the most common endocrine disorders observed in patients with CHF, particularly in individuals with reduced ejection fraction, aiming to qualify the risks, quantify the epidemiological burden and discuss about the potential role of endocrine treatment. Thyroid dysfunction is commonly observed in patients with CHF, and sometimes it could be the consequence of certain medications (e.g., amiodarone). Male and female hypogonadism may also coexist in this clinical context, contributing to deteriorating the prognosis of these patients. Furthermore, growth hormone deficiency may affect the development of adult myocardium and predispose to CHF. Limited recommendation suggests to screen endocrine disorders in CHF patients, but it could be interesting to evaluate possible endocrine dysfunction in this setting, especially when a high suspicion coexists. Data referring to long-term safety and effectiveness of endocrine treatments in patients with CHF are limited, and their impact on several “hard” endpoints (such as hospital admission, all-cause, and cardiovascular mortality) are still poorly understood.
In the essential homeostatic role of kidney, two intrarenal mechanisms are prominent: the glomerulotubular balance driving the process of Na+ and water reabsorption in the proximal tubule, and the ...tubuloglomerular feedback which senses the Na+ concentration in the filtrate by the juxtaglomerular apparatus to provide negative feedback on the glomerular filtration rate. In essence, the two mechanisms regulate renal oxygen consumption. The renal hyperfiltration driven by increased glomerular filtration pressure and by glucose diuresis can affect renal O2 consumption that unleashes detrimental sympathetic activation. The sodium-glucose co-transporters inhibitors (SGLTi) can rebalance the reabsorption of Na+ coupled with glucose and can restore renal O2 demand, diminishing neuroendocrine activation. Large randomized controlled studies performed in diabetic subjects, in heart failure, and in populations with chronic kidney disease with and without diabetes, concordantly address effective action on heart failure exacerbations and renal adverse outcomes.
Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk ...of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF.
We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF.
Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4;
for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease.
In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.
•Congestion in acute heart failure affects survival curves and length of stay.•Our comparisons revealed that the higher the hydration status, the longer the LOS.•BIVA measurements are independent ...predictor of length of stay in acute HF patients.
Congestion in acute heart failure (AHF) affects survival curves and hospital length of stay (LOS). The evaluation of congestion, however, is not totally objective. The aim of this study was to verify the accuracy of bioelectrical impedance vector analysis (BIVA) in predicting the LOS in AHF patients.
This is a retrospective study. A total of 706 patients (367 male; mean age: 78 ± 10 y) who had been admitted to hospital with an AHF event were enrolled. All underwent anthropometric and clinical evaluation, baseline transthoracic echocardiography, and biochemical and BIVA evaluations.
The comparison among the clinical characteristics of congestion, LOS, and hyperhydration status revealed that the higher the hydration status, the longer the LOS (from 7.36 d interquartile range: 7.34–7.39 d in normohydrated patients to 9.04 d interquartile range: 8.85– 9.19 d in severe hyperhydrated patients; P < 0.05). At univariate analysis, brain natriuretic peptide, blood urea nitrogen, New York Heart Association class, hemoglobin, hydration index, and peripheral edema all had a statistically significant influence on LOS. At multivariate analysis, only brain natriuretic peptide (P < 0.0001), blood urea nitrogen (P = 0.011), and hydration index (P < 0.0001) were significantly associated to LOS.
Congestion evaluated by BIVA is an independent predictor of length of total hospital stay in HF patients with acute decompensation. The quick and reliable detection of congestion permits the administration of target therapy for AHF, thus reducing LOS and treatment costs.
The kidneys and heart work together to balance the body's circulation, and although their physiology is based on strict inter dependence, their performance fulfills different aims. While the heart ...can rapidly increase its own oxygen consumption to comply with the wide changes in metabolic demand linked to body function, the kidneys physiology are primarily designed to maintain a stable metabolic rate and have a limited capacity to cope with any steep increase in renal metabolism. In the kidneys, glomerular population filters a large amount of blood and the tubular system has been programmed to reabsorb 99% of filtrate by reabsorbing sodium together with other filtered substances, including all glucose molecules. Glucose reabsorption involves the sodium-glucose cotransporters SGLT2 and SGLT1 on the apical membrane in the proximal tubular section; it also enhances bicarbonate formation so as to preserve the acid-base balance. The complex work of reabsorption in the kidney is the main factor in renal oxygen consumption; analysis of the renal glucose transport in disease states provides a better understanding of the renal physiology changes that occur when clinical conditions alter the neurohormonal response leading to an increase in glomerular filtration pressure. In this circumstance, glomerular hyperfiltration occurs, imposing a higher metabolic demand on kidney physiology and causing progressive renal impairment. Albumin urination is the warning signal of renal engagement over exertion and most frequently heralds heart failure development, regardless of disease etiology. The review analyzes the mechanisms linked to renal oxygen consumption, focusing on sodium-glucose management.
Abstract
Takotsubo syndrome (TTS) is an acute heart failure syndrome with significant rates of in and out-of-hospital mayor cardiac adverse events (MACE). To evaluate the possible role of neoplastic ...biomarkers CA-15.3, CA-19.9 and Carcinoembryonic Antigen (CEA) as prognostic marker at short- and long-term follow-up in subjects with TTS. Ninety consecutive subjects with TTS were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9 and CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded. Forty-three (46%) patients experienced MACE during hospitalization. These patients had increased admission levels of CEA (4.3 ± 6.2 vs. 2.2 ± 1.5 ng/mL,
p
= 0.03). CEA levels were higher in subjects with in-hospital MACE. At long term follow-up, CEA and CA-19.9 levels were associated with increased risk of death (log rank
p
< 0.01, HR = 5.3, 95% CI 1.9–14.8, HR = 7.8 95% CI 2.4–25.1, respectively,
p
< 0.01). At multivariable analysis levels higher than median of CEA, CA-19.9 or both were independent predictors of death at long term (Log-Rank
p
< 0.01). Having both CEA and CA-19.9 levels above median (> 2 ng/mL, > 8 UI/mL respectively) was associated with an increased risk of mortality of 11.8 (95% CI 2.6–52.5,
p
= 0.001) at follow up. Increased CEA and CA-19.9 serum levels are associated with higher risk of death at long-term follow up in patients with TTS. CEA serum levels are correlated with in-hospital MACE.
Impaired pulmonary circulation hemodynamics are characteristic of pulmonary hypertension (PH). We therefore sought to evaluate possible correlations between endothelial function noninvasively ...assessed by brachial artery flow-mediated dilation (FMD) and hemodynamic parameters at right-sided cardiac catheterization in patients with clinically suspected PH. Consecutive outpatients with suspected PH were enrolled in the study. In all patients, endothelial function was assessed by FMD and hemodynamic parameters (pulmonary artery pressure PAP); pulmonary vascular resistances PVR) were derived by right-sided cardiac catheterization. For this study, 95 consecutive patients with suspected PH were enrolled (mean age 63 ± 13 years, 58% male) and included in the analysis. FMD values were significantly correlated with systolic (s)PAP levels (r = −0.29, p = 0.016); correlation with PVR was of borderline significance (r = −0.21, p = 0.78). After multivariable regression analysis including age, gender, tricuspid annular plane systolic excursion and peak tricuspid regurgitation velocity (peak TRV), and FMD, the latter remained significantly correlated with systolic pulmonary artery pressure (sPAP) values (B = −47, p = 0.02). After classifying patients according to median levels of peak TRV and FMD into 3 groups (neither, either, or both impaired), progressively increased levels of sPAP, mean PAP, and PVR were found (p for trend <0.001 in all cases). FMD values were inversely related to sPAP levels in a small population of patients with clinically suspected PH. In combination with peak TRV levels, FMD values noninvasively assessed were predictive of increased sPAP, mean PAP, and PVR.
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