Moderate Chronic Heart Failure Research Articles

Renin-angiotensin system inhibitors for patients with mild or moderate chronic kidney disease and heart failure with mildly reduced or preserved ejection fraction

BackgroundRenin-angiotensin system inhibitors (RASI) reduce adverse cardiovascular events in patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤40% and mild or moderate chronic kidney disease (CKD). However, RASI administration rate and its association with long-term outcomes in patients with CKD complicated by HF with LVEF >40% remain unclear. MethodsWe analyzed 1923 consecutive patients with LVEF >40% registered within the multicenter database for hospitalized HF. We assessed RASI administration rate and its association with all-cause mortality among patients with mild or moderate CKD (estimated glomerular filtration rate [eGFR]: 30–60 mL/min/1.73 m2). Exploratory subgroups included patients grouped by age (<80, ≥80 years), sex, previous HF hospitalization, B-type natriuretic peptide (higher, lower than median), eGFR (30–44, 45–59 mL/min/1.73 m2), systolic blood pressure (<120, ≥120 mmHg), LVEF (41–49, ≥50%), and mineralocorticoid receptor antagonists (MRA) use. ResultsAmong patients with LVEF >40%, 980 (51.0%) had mild or moderate CKD (age: 81 [74–86] years; male, 52.6%; hypertension, 69.7%; diabetes, 25.9%), and 370 (37.8%) did not receive RASI. RASI use was associated with hypertension, absence of atrial fibrillation, and MRA use. After multivariable adjustments, RASI use was independently associated with lower all-cause mortality over a 2-year median follow-up (hazard ratio: 0.58, 95% confidence interval: 0.43–0.79, P = 0.001), and the mortality rate difference was predominantly due to cardiac death, consistent in all subgroups. ConclusionsApproximately one-third of HF patients with mild or moderate CKD and LVEF >40% were discharged without RASI administration and demonstrated relatively guarded outcomes.

Galectin -3: an independent cardiac marker of left ventricular (LV) remodeling in chronic heart failure

Introduction and Aim: Heart failure (HF) with increased morbidity and mortality is a critical condition where the cardiac pumping capacity fails to meet up with the body’s demand. Its development is silent due to slow, progressive remodeling presenting with symptoms later. Brain Natriuretic peptides (BNP) denotes ventricular loading status which do not reveal other mechanisms whereas a novel marker Galectin-3 (Gal-3) provides information about cardiac structural changes which includes inflammation, fibrosis, remodeling for guiding treatment. Research studies demonstrated that there is upregulation of Galectin- 3 in both acute and chronic heart failure (CHF) individuals. The objectives of our study were to compare Galectin- 3 levels in moderate and severe LVD CHF patients and determine whether serum Galectin -3 can be used as an independent cardiac marker of ventricular structural remodeling in such HF individuals. Materials and Methods: 80 patients between 20 - 80 years diagnosed with CHF using Framingham criteria with ejection fraction (EF) of 45% and classified into two groups:(i) moderate LVD and (ii) severe LVD. Those with abnormal kidney functions were excluded. Comparison was done between serum Galectin - 3 and BNP; Gal- 3 was determined to be an independent marker of structural remodeling of LV between the two categories. Results: Galectin-3 and BNP were significantly increased in HF with severe LVD than moderate LVD. Multivariate linear regression showed Galectin-3 as an independent predictor of LV remodeling with respect to changes in LV end- diastolic dimension with statistically significant p 0.001 whereas BNP did not show any such significance. Conclusion: Galectin -3 and BNP levels were elevated in severe LV dysfunction than moderate LVD and concluded that Gal-3 is an independent cardiac biomarker of LV remodeling in Chronic heart failure.

Clinical and Echocardiographic Correlates of Iron Status in Chronic Heart Failure Patients: A Cross-Sectional Descriptive Study.

Chronic heart failure (HF) is one of the conditions commonly seen in the medical outpatient departments, and iron deficiency (ID) has been reported as the commonest nutritional deficiency in these patients. The presence of ID may interfere with the clinical parameters of chronic HF. The relationship between iron status and chronic HF needs more attention and should be given more consideration in the evaluation of patients with chronic HF. The aim of the study was to determine the relationship, if any, between iron status and clinical/echocardiographic variables in chronic HF. A cross-sectional descriptive study was carried out at the Lagos University Teaching Hospital (LUTH), Nigeria, where 88 patients with chronic HF were recruited to participate in this study. The participants underwent clinical and laboratory assessments. Iron status was assessed with full blood count parameters; serum ferritin and transferrin saturation (Tsat) and its relationship with clinical parameters among these participants were also studied. No correlations existed between the duration of chronic HF and iron status when compared using Tsat. However, a significant weak negative correlation was observed between the duration of HF and the serum ferritin levels. The clinical characteristics of the HF participants with and without ID were compared. There was no significant difference in the frequency of prior hospitalization in both groups. However, a higher proportion of participants with severe HF (New York Heart Association (NYHA) classes III/IV) (n = 14; 46.7%) were iron-deficient compared to those with moderate chronic HF (NYHA II) (n = 11; 36.7%). This relationship was statistically significant. Left ventricular ejection fraction (LVEF) was similar in the iron-deficient and iron-replete groups (using serum ferritin or Tsat) both when compared as means and when compared after categorizing LVEF as HF with preserved ejection fraction (HFpEF) vs HF with reduced ejection fraction (HFrEF). There was no statistically significant correlation between the severity of ID and LVEF. Conclusion: A spectrum of clinical changes occurs in patients with chronic HF. ID can make these changes more profound and the condition less amenable to standard HF treatments. These patients may therefore benefit from further evaluation for this nutritional deficiency. Laboratory measurements including Tsat and serum ferritin may help in further assessment of select patients with worse and/or non-responsiveclinical parameters.

The Efficacy and Safety of Bisoprolol in the Treatment of Myocardial Infarction with Cardiac Insufficiency.

Bisoprolol is commonly used to treat moderate or severe chronic stable heart failure, coronary heart disease, and hypertension. This study is aimed at analyzing the efficacy of bisoprolol in the treatment of myocardial infarction with cardiac insufficiency and its effect on cardiac function, Hcy, and CRP through meta-analysis. A total of 120 patients with myocardial infarction and cardiac insufficiency from February 2020 to February 2021 were selected and randomly divided into two groups (control and the observation, n = 60) according to the random number table method. The control group was given conventional treatment. The observation group was given bisoprolol on the basis of control group. The clinical efficacy, systolic blood pressure, diastolic blood pressure, heart rate, cardiac function indexes, homocysteine (Hcy), and C-reactive protein (CRP) levels were compared between the two groups before and after treatment through data analysis. Adverse reactions were observed during treatment. Compared with the control group, the total effective rate of the observation group was significantly increased (p < 0.05). After treatment, the levels of heart rate, left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) and serum Hcy and CRP levels in the observation group were significantly lower than those in the control group (p < 0.05). Meanwhile, left ventricular ejection fraction (LVEF) level in the observation group after treatment was higher than that of the control group (p < 0.05). Bisoprolol combined with conventional treatment can reduce serum Hcy and CRP levels in patients with myocardial infarction and cardiac insufficiency and improve cardiac function. Moreover, there are no obvious adverse reactions during the treatment.

Diabetes mellitus type 2: the relationship of baseline clinical, laboratory and echocardiographic parameters with long-term major adverse cardiovascular events

Background : Type 2 diabetes mellitus (T2DM) increases the risk of developing cardiovascular disease. The search for factors interrelated with the development of major adverse cardiovascular events (MACE) in patients with T2DM over a long period of observation is urgent. Aim : To reveal the relationship of clinical, laboratory and echocardiographic parameters with the development of long-term MACE in T2DM. Materials and methods : 94 patients with T2DM (mean age — 55,3 ± 5,5 years, 65% of women) without manifestations of moderate and severe chronic heart failure (CHF), impaired renal function, severe somatic pathology underwent a ­complete clinical and laboratory examination. Echocardiography and 6-minute walk test (6mwt) were performed. The plasma level of the N-terminal propeptide of natriuretic hormone B-type (NT-proBNP) was determined. The variability of fasting blood glucose and intraday glycemic variability were measured by calculating the standard deviation (SD) and the coefficient of variation (CV) of at least 3 blood glucose values for 3 days. Analysis of MACE (death from any cause, myocardial infarction, stroke, decompensation of CHF, myocardial revascularization for emergency indications) was performed after 8,8 ± 0,72 years ( n=88 ). Patients with T2DM were divided into 2 groups — without MACE (group 1, n=54) and with MACE (group 2, n=34). The search for predictors of long-term MACE in T2DM was carried out using the method of logistic regression. Results : Initially, group 2 differed from group 1 in a longer duration of T2DM, a higher incidence of stable coronary heart disease (55,9% vs 27,8%, p = 0,008), a higher presence of albuminuria&gt;30 mg/day (66,7% vs 37,3% , p=0,008), a higher presence of initial symptoms of CHF (67,8% vs 21,8%, p=0,001), greater fasting glucose variability (SD 2,07 mmol/l vs 1,2 mmol/l, p=0,003), greater intraday glucose variability (SD 2,3 mmol/l vs 1,6 mmol/l, p=0,001, CV 28,2% vs 18,8%, p=0,001), higher levels of NT-proBNP (46,9 pg/ml vs 24,2 pg/ml, p=0,012), larger left atrial size (4,4 cm vs 4,1 cm, p=0,039), shorter 6mwt distance. The logistic regression method revealed the parameters that are most interconnected with long-term MACE in T2DM: intraday glycemic CV (p=0,0012), left atrial size (p=0,02) and initial manifestations of CHF (p=0,03). Conclusion : The development of long-term MACE in T2DM is associated with an increase in gl ycemic variability, an increase in NT-proBNP level, an increase in the left atrial size, and a decrease in exercise tolerance. According to logistic regression data, the most significant indicators associated with adverse outcomes are an increase in intraday glycemic CV, an increase in the left atrial size, and the presence of initial symptoms of CHF.

Right ventricular diastolic dysfunction in patients with coronary artery disease: frequency and associated factors

Abstract Funding Acknowledgements Type of funding sources: None. Background. The prognostic value of right ventricle (RV) systolic dysfunction is known. Nearly all data on the importance of right ventricle function is notably focused on its systolic dysfunction, while right ventricle filling is far less studied, perhaps because of challenges in diastolic dysfunction assessment [1]. Independent prognostic value of RV diastolic dysfunction (RVDD) has been identified in certain clinical situations [2], but these studies are few in number. Therefore it is important to continue investigating the right ventricle diastolic function and clarify its possible clinical and prognostic significance in various groups of patients [3]. Thus, the purpose of this study was to assess the incidence of RVDD in patients with coronary artery disease (CAD) and to identify factors associated with its presence. Material and Methods 200 patients with stable CAD (153 men) were enrolled in the study. Echocardiography was performed on a Vivid S5 ultrasound scanner (GE). We studied clinical data, left ventricular indices, RV systolic and diastolic parameters (Et, At, et", a"t, s"t, TAPSE, and RV Tei index). Depending on the presence or absence of RVDD, all patients were divided into 2 groups: Group 1 - patients with RVDD (n = 92; 64 [61; 69] years; 73 (79.4%) men) and Group 2 - patients without RVDD (n = 108; 63 [60; 67] years; 80 (74.0%) men). Results. The RV diastolic dysfunction is much more common than its systolic dysfunction in patients with stable CAD (46% and 7.5%, respectively, Fig. 1). Old myocardial infarction (MI) (p = 0.007), anterior MI (p = 0.001), congestive heart failure (p = 0.030) and peripheral arterial disease (p = 0.030) were more prevalent in patients with RVDD. The end-systolic dimension were higher (p = 0.010), while left ventricular (LV) ejection fraction (EF) (p = 0.044) and the mitral E/A ratio (p &amp;lt; 0.001) were lower in this group. No significant differences were found between groups in the coronary artery stenosis. Independent predictors of the RVDD presence were increased age, old MI, hyperlipidemia, moderate chronic heart failure, peripheral arterial disease, and decreased LVEF. ROC-curves of studied left ventricular variables (LVEF, ratio E/A and E/e’) association with RVDD is presented in Fig. 2. The areas under the curves were less than 0.7 for all variables, which indicated an unacceptable ability to distinguish. Conclusions. The RV diastolic dysfunction is much more common than its systolic dysfunction in patients with stable CAD. The RVDD presence was predominantly associated with an increase in age and LV systolic dysfunction, but not with coronary artery lesions. The predictive value of RVDD requires further research. Abstract Figure. Abstract Figure.

Reduced LVEDD following a 12 week exercise training program in patients with symptomatic chronic heart failure is associated with reduction in serum levels of Troponin I

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Norwegian University of Science and Technology Danish Research Council Background Exercise training (ET) exerts many beneficial effects on the cardiovascular system, and longitudinal observational data from epidemiological studies suggest that higher physical activity is associated with lower concentrations of cardiac troponins. We have previously shown that ET can reduce Left Ventricle End-diastolic diameter (LVEDD), and improve exercise capacity. Purpose Our aim was to explore the relationship between changes in LVEDD and changes in high-sensitive plasma troponin I (hs-TnI) levels in patients with symptomatic heart failure undergoing a 12 week structured exercise training program in the randomized multicenter SMARTEX trial. Methods This was a post hoc analysis in 199 patients with symptomatic HF with LVEF &amp;lt;35% and NYHA II-III that were randomly assigned to High Intensity Interval Training (HIIT, n = 73), Moderate Continuous Training (MCT, n = 59) or Recommendation of Regular Exercise, (RRT, n = 67) for 12 weeks. Log-transformed Hs-TnI measurements and clinical data acquired before (BL) and after a 12 week exercise training intervention (12 weeks) and at 1 year follow-up (1 year) were analysed using a linear mixed model. For Troponin analysis the STAT Troponin-I from Abbott Diagnostics was used. Nakagawa’s marginal R2 and conditional R2 were used to evaluate variance explained by fixed effects only and by fixed and random effects together, respectively. Changes of LVEDD between baseline and 12 weeks and baseline and 52 weeks were evaluated using linear mixed model. The outcome variable were measures of LVEDD, while age, sex, visit and training group and their interaction [visit × training group] were included as fixed effects. Patient id and training center were random effects. Covariance structure was compound symmetry. Linear association between log-transformed TnI and LVEDD baseline was evaluated using Pearson correlation coefficient (R). Results Serum was available for hs-TnI analyses in 199 patients. In the HIIT group there was a sustained significant reduction in LVEDD at both 12 and 52 weeks. In the MCT group this reduction was statistically significant at 52 weeks only. Mixed model analysis predicts that each 1 mm decrease in LVEDD is associated with 1.2% decrease in TnI levels (95% CI: 0.6 – 1.9%, p &amp;lt;0.001). Neither time nor training group were associated with changes of TnI (overall test p = 0.739 and p = 0.987, respectively). Dynamics of TnI is highly patient-specific with Intraclass correlation coefficient (ICC) = 0.86. Mixed model explains 87% variation of the data (conditional R2), however, only 7% is attributed to the fixed effects (marginal R2). At baseline, TnI and LVEDD have modest but statistically significant correlation (R = 0.2, p= 0.004). Conclusions A reduction of LVEDD following a 12-week exercise-training program is associated with a reduction in plasma troponin levels, in patients with mild to moderate chronic heart failure. Abstract Figure.

Impaired right ventricular filling in patients with a chronic coronary syndrome.

The prognostic value of right ventricle (RV) systolic dysfunction is known but the RV diastolic dysfunction (RVDD) is less investigated, thus the purpose of this study was to assess the incidence of RVDD in patients with coronary artery disease (CAD) and to identify factors associated with its presence. We examined 200 patients with stable CAD (153 men). RV diastolic parameters were studied by echocardiography: peak velocity of early (Et) and late (At) RV fill-ing and their ratio, velocities at the tricuspid annulus (et', a't, s't). Patients were divided into 2 groups: with (n=92) and without RVDD (n=108). Old myocardial infarction (MI) (p=0.007), anterior MI (p=0.001), congestive heart failure (p=0.030) and peripheral arterial disease (p=0.030) were more prevalent in patients with RVDD. The end-systolic dimensions were higher (p=0.010), while left ventricular (LV) ejection fraction (EF) (p=0.044) and the mitral E/A ratio (p<0.001) were lower in this group. No significant differences were found between the groups in the coronary artery stenosis. Independent predictors of the RVDD presence were increased age, old MI, hyperlipidemia, moderate chronic heart failure, peripheral arterial disease, and decreased LVEF. The RV diastolic dysfunction is much more common than systolic dysfunction in patients with stable CAD (46% and 7.5%, respectively). The RVDD presence was predominantly associated with an increase in age and LV systolic dysfunction, but not with coronary artery lesions. The predictive value of RVDD requires further research.

The Use of a New Type of Heart Rate-controlled Training System HeartGo® for Patients with Chronic Heart Failure on the Pedelec

Background: Exercise Training is beneficial in heart failure patients, while training opportunities are limited. Pedelecs represent a novel training possibility for these patients, while safety and efficacy of pedelec training in heart failure is unknown. Therefore, we conducted a pilot study to address these issues. The study “HI-Herz.BIKE Saar” (August 2017 - September 2019) examined the health benefits and training effects of e-bikes (pedelecs) in patients from ambulatory heart groups with moderate chronic heart failure (CHI). Methods: Ten subjects with a strictly defined NYHA stage II-III heart failure and a LVEF of ?50% were selected. The presented clinical study is explicitly marked as a pilot study, as a new, so far not tested technique was used for exercise control. When selecting the heart failure patients defined in this way, a higher number of subjects could not be reached at only one study center. Participants cycled once weekly for 60-150 min and 20-50 km with a follow-up of 2 years as detailed in the Methods section. The new HeartGo® system used here for the first time allows heart rate- controlled training on a special pedelec via a smartphone app. The groups were accompanied during the training rides by a doctor and a paramedic. The training units were increased in duration, distance, and target frequency every six months. Frequency behavior, pedaling and motor load on the pedelec as well as clinical data such as ejection fraction, a biomarker (NT-pro BNP), risk factors, arterial blood pressure, and ergometric tests were measured.

New approach for the rehabilitation of patients with chronic heart failure associated with type 2 diabetes

Rationale. Coronary artery disease (CAD) is the most common cardiovascular disease, being responsible for the largest number of deaths and disabilities. The use of lipid-lowering drugs is one of the most important aspects of pharmacological rehabilitation of patients with CAD. Objective of the work . Study the features of pharmacological rehabilitation of patients with chronic heart failure (CHF) associated with type 2 diabetes mellitus (DM) using a combination therapy of lipid-lowering Ezetimibe and Rosuvastatin. Materials and methods. 70 patients with coronary artery disease with a clinical picture of moderate CHF and concomitant type 2 diabetes were enrolled in the study. The patients enrolled in the study were recommended to change their lifestyle, including quitting smoking, increasing physical activity, and adhering to a cholesterol-free diet. After a month, the patients were divided into 2 groups of 35 people each by a simple randomization method. The comparison group (n = 35) received a combination of Rosuvastatin 20 mg/day and Ezetimibe 10 mg/day, the control group (n = 35) received only Rosuvastatin 20 mg/day. The duration of the study was 12 months. The follow-up visits were scheduled at 1, 3, 6 and 12 months after they started taking drugs. Results. At the end of the study, there were no statistically significant differences between the study groups in the number of adverse cardiovascular events (14.3% vs 20.0%, respectively, p = 0.751). There were differences in the total number of hospitalizations caused by cardiovascular diseases (14.3% vs 40%, respectively, p = 0.032). Conclusions . The prescription of combination lipidemic therapy with Rosuvastatin at a dose of 20 mg/day and Ezetimibe at a dose of 10 mg/day results in decreased hospitalizations caused by cardiovascular diseases.

Sodium-glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus.

The management of type 2 diabetes mellitus (T2DM) is becoming increasingly complex. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are the newest antidiabetic agents for T2DM. By targeting the kidney, they have a unique mechanism of action, which results in enhanced glucosuria, osmotic diuresis and natriuresis, thereby improving glucose control with a limited risk of hypoglycaemia and exerting additional positive effects such as weight loss and the lowering of blood pressure. Several outcome studies with canagliflozin, dapagliflozin or empagliflozin reported a statistically significant reduction in major cardiovascular events, hospitalization for heart failure and progression to advanced renal disease in patients with T2DM who have established atherosclerotic cardiovascular disease, several cardiovascular risk factors, albuminuric mild to moderate chronic kidney disease or heart failure. Current guidelines proposed a new paradigm in the management of T2DM, with a preferential place for SGLT2is, after metformin, in patients with atherosclerotic cardiovascular disease, heart failure and progressive kidney disease. Ongoing trials might extend the therapeutic potential of SGLT2is in patients with, but also without, T2DM. This Review provides an update of the current knowledge on SGLT2is, moving from their use as glucose-lowering medications to their new positioning as cardiovascular and renal protective agents.

PCV48 COST EFFECTIVENESS OF RIVAROXABAN IN CORONARY ARTERY DISEASE AND/OR PERIPHERAL ARTERY DISEASE FOR 5 DIFFEREN PATIENT SUB-GROUPS IN TURKEY

Rivaroxaban has clinical benefits in the prevention of atherothrombotic events in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD) based on the results of the COMPASS study. The aim of this study is to understand the cost and clinical benefits of rivaroxaban compared to aspirin from the perspective of reimbursement agency including direct costs and clinical trial outcomes for subgroups in Turkey. A Markov model simulation has been conducted based on the COMPASS study results and published cost data. An expert survey has been conducted for understanding gaps of the cost of each event and health state with 5 experts (3 cardiologists & 2 health economists). Cost of each event and health state has been calculated based on expert survey and Social Security Institution`s reimbursement list. Subgroups have been set as coronary artery disease (CAD), peripheral artery disease (PAD), CAD and PAD, CAD and moderate renal impairment, CAD and Chronic Heart Failure (HF). Time horizon of the model was selected as 30 years. Willingness to pay (WTP) ratio has been accepted as 3 times gross domestic product (GDP) as 145.000 Turkish Lira (TL) depending on World Health Organization`s guideline. Rivaroxaban has been shown to be cost effective in all subgroups with incremental cost effectiveness ratio (ICER) ranging from 8.888 TL to 130.042 TL per life year as being under WTP ratio. The ICER decreases in subgroups with comorbidities. The cost-effectiveness analysis shows that rivaroxaban is cost-effective under the given indications. Decision makers need to consider the study results for achieving better outcomes in CAD and/or PAD patients.

Relationship of High Circulating Cystatin C to Biochemical Markers of Bone Turnover and Bone Mineral Density in Elderly Males with a Chronic Heart Failure.

SummaryBackgroundThe aim of the study was to investigate the association of Cystatin C (CysC) to biochemical markers of bone turnover and bone mass, and to evaluate its prognostic significance in elderly males with chronic heart failure (CHF).MethodsA prospective cohort study was executed on sixtyeight males (mean age 68±7 years) with mild to moderate CHF, together with 19 of corresponding age- and body mass index-matched healthy individuals who underwent cardio vascular, bone mineral density (BMD), and body com position assessment. Biochemical assessment of all subjects included NT-pro-BNP, parathyroid hormone (PTH), 25-hydroxy vitamin D (25(OH)D), CysC, and biochemical markers of bone turnover including osteocalcin (OC), alkaline phosphatase (ALP), β-CrossLaps (β-CTx), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL).ResultsSerum CysC was significantly increased in males with CHF in comparison to healthy control ones. A significant positive association was found between CysC levels and OC in males with CHF, while OC and β-CTx increased in increasing CysC tertiles. In multivariate regression analysis, OC and smoking were a significant determinant of CysC in males with CHF. Level of CysC was found to be positively associated with an increased fatal risk in males with CHF.ConclusionsSerum osteocalcin is an independent predictor of CysC level in elderly males with CHF. Higher CysC level showed a negative relation to survival and bone loss in males with CHF. Further research is needed to confirm the potential role of CysC in the crosstalk between heart, kidney, bone, and energy metabolism in CHF.

Relationship of High Circulating Cystatin C to Biochemical Markers of Bone Turnover and Bone Mineral Density in Elderly Males with a Chronic Heart Failure

SummaryBackground:The aim of the study was to investigate the association of Cystatin C (CysC) to biochemical markers of bone turnover and bone mass, and to evaluate its prognostic significance in elderly males with chronic heart failure (CHF).Methods:A prospective cohort study was executed on sixtyeight males (mean age 68±7 years) with mild to moderate CHF, together with 19 of corresponding age- and body mass index-matched healthy individuals who underwent cardio vascular, bone mineral density (BMD), and body com position assessment. Biochemical assessment of all subjects included NT-pro-BNP, parathyroid hormone (PTH), 25-hydroxy vitamin D (25(OH)D), CysC, and biochemical markers of bone turnover including osteocalcin (OC), alkaline phosphatase (ALP), β-CrossLaps (β-CTx), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL).Results:Serum CysC was significantly increased in males with CHF in comparison to healthy control ones. A significant positive association was found between CysC levels and OC in males with CHF, while OC and β-CTx increased in increasing CysC tertiles. In multivariate regression analysis, OC and smoking were a significant determinant of CysC in males with CHF. Level of CysC was found to be positively associated with an increased fatal risk in males with CHF.Conclusions:Serum osteocalcin is an independent predictor of CysC level in elderly males with CHF. Higher CysC level showed a negative relation to survival and bone loss in males with CHF. Further research is needed to confirm the potential role of CysC in the crosstalk between heart, kidney, bone, and energy metabolism in CHF.

Overnight Pulse Oximetry Unwoven.

Overnight Pulse Oximetry Unwoven.

Soluble ST2 protein and hospitalizations due to worsening chronic heart failure during a one-year follow-up in a population with reduced ejection fraction.

Hospitalizations due to worsening chronic heart failure (CHF) are common. However, the relationship between a single measurement of soluble ST2 protein (sST2) and the necessity of hospitalization in CHF is still unclear. The aim of this study was to determine the association between a single measurement of sST2 concentration and hospitalizations due to worsening CHF during a one-year follow-up. The study involved 167 consecutive patients (mean age 63 years, 83% males) with CHF in stable NYHA classes I-III with left ventricular ejection fraction (LVEF) ≤ 45% (median 29.65%, range 13-45%). Fifty-six variables were analyzed (clinical factors, basic laboratory results on admission, standard 12-lead ECG, echocardiography and coronary arteriography results). Information about hospitalizations due to worsening CHF was obtained during telephone interviews conducted 12 months after discharge from the cardiac ward. In order to define factors associated with hospitalization, uniand multivariate regression analyses were performed. A total of 53 patients from the study group (38%) were hospitalized due to worsening CHF. They included a higher percentage of males (p = 0.042), higher concentrations of sST2 (p = 0.049), and glucose (p = 0.010). The multivariate analysis (for model χ2 = 17.235; p < 0.001) revealed that glucose and sST2 were independently associated with hospitalization due to worsening CHF during the 1-year observation (p < 0.001). In patients with stable mild to moderate CHF with reduced EF, a single measurement of sST2 protein and glucose were independent variables for hospitalization due to worsening CHF over a 1-year follow-up period. The defined prognostic model including sST2 and fasting glucose better identified patients without HF-related hospitalizations.

Electrical and mechanical alternans during ventricular tachycardia with moderate chronic heart failure

A chronic heart failure (CHF) rat underwent epicardial programmed electrical stimulation (PES). Ventricular tachycardia (VT) developed during PES. Mechanical alternans was noted despite fixed tachycardia cycle length. Anti-tachycardia pacing attempts initiated a second VT that generated pulse intermittently and then degenerated into pulseless VT with electrical alternans.To our knowledge electrical and mechanical alternans have not been recorded in animal models of CHF during VT. The distinct events of mechanical alternans and electrical alternans may be indicative of progressively worsened calcium handling in the compromised cardiomyocytes.Although ion channel differences between rodents and humans exist, this work attempts to demonstrate this rat model's usefulness in understanding cardiac electrophysiology in CHF.

Doppler Assessment of Diastolic Function Reflect the Severity of Injury in Rats With Chronic Heart Failure

ObjectiveFor chronic heart failure (CHF), more emphasis has been placed on evaluation of systolic as opposed to diastolic function. Within the study of diastology, measurements of left ventricular (LV) longitudinal myocardial relaxation have the most validation. Anterior wall radial myocardial tissue relaxation velocities along with mitral valve inflow (MVI) patterns are applicable diastolic parameters in the differentiation between moderate and severe disease in the ischemic rat model of CHF. Myocardial tissue relaxation velocities correlate with traditional measurements of diastolic function (ie, hemodynamics, Tau, and diastolic pressure-volume relationships). Methods and ResultsMale Sprague-Dawley rats underwent left coronary artery ligation or sham operation. Echocardiography was performed at 3 and 6 weeks after coronary ligation to evaluate LV ejection fraction (EF) and LV diastolic function through MVI patterns (E, A, and E/A) and Doppler imaging of the anterior wall (e′ and a′). The rats were categorized into moderate or severe CHF according to their LV EF at 3 weeks postligation. Invasive hemodynamic measurements with solid-state pressure catheters were obtained at the 6-week endpoint. Moderate (N = 20) and severe CHF (N = 22) rats had significantly (P < .05) different EFs, hemodynamics, and diastolic pressure-volume relationships. Early diastolic anterior wall radial relaxation velocities as well as E/e′ ratios separated moderate from severe CHF and both diastolic parameters had strong correlations with invasive hemodynamic measurements of diastolic function. ConclusionRadial anterior wall e′ and E/e′ can be used for serial assessment of diastolic function in rats with moderate and severe CHF.

Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure.

Chronic heart failure (CHF) reduces nitric oxide (NO) bioavailability and impairs skeletal muscle vascular control during exercise. Reduction of NO2 (-) to NO may impact exercise-induced hyperemia, particularly in muscles with pathologically reduced O2 delivery. We tested the hypothesis that NO2 (-) infusion would increase exercising skeletal muscle blood flow (BF) and vascular conductance (VC) in CHF rats with a preferential effect in muscles composed primarily of type IIb + IId/x fibers. CHF (coronary artery ligation) was induced in adult male Sprague-Dawley rats. After a >21-day recovery, mean arterial pressure (MAP; carotid artery catheter) and skeletal muscle BF (radiolabeled microspheres) were measured during treadmill exercise (20 m/min, 5% incline) with and without NO2 (-) infusion. The myocardial infarct size (35 ± 3%) indicated moderate CHF. NO2 (-) infusion increased total hindlimb skeletal muscle VC (CHF: 0.85 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1) and CHF + NO2 (-): 0.93 ± 0.09 ml·min(-1)·100 g(-1)·mmHg(-1), P < 0.05) without changing MAP (CHF: 123 ± 4 mmHg and CHF + NO2 (-): 120 ± 4 mmHg, P = 0.17). Total hindlimb skeletal muscle BF was not significantly different (CHF: 102 ± 7 and CHF + NO2 (-): 109 ± 7 ml·min(-1)·100 g(-1) ml·min(-1)·100 g(-1), P > 0.05). BF increased in 6 (∼21%) and VC in 8 (∼29%) of the 28 individual muscles and muscle parts. Muscles and muscle portions exhibiting greater BF and VC after NO2 (-) infusion comprised ≥63% type IIb + IId/x muscle fibers. These data demonstrate that NO2 (-) infusion can augment skeletal muscle vascular control during exercise in CHF rats. Given the targeted effects shown herein, a NO2 (-)-based therapy may provide an attractive "needs-based" approach for treatment of the vascular dysfunction in CHF.

A physiologically based pharmacokinetic drug-disease model to predict carvedilol exposure in adult and paediatric heart failure patients by incorporating pathophysiological changes in hepatic and renal blood flows.

Background and ObjectiveChronic diseases are associated with pathophysiological changes that could have profound impacts on drug pharmacokinetic behaviour, with a potential need to modify the administered drug therapy. It is important to acknowledge that most patients with chronic illnesses do not have a single, predominant condition but suffer from multiple comorbidities. The rapid advancement in physiologically based pharmacokinetic (PBPK) modelling, as well as the increasing quantitative knowledge of disease-related pathophysiological changes, facilitate building of drug–disease models. However, there are only a few published examples of PBPK models incorporating the pathophysiological changes that occur with chronic diseases. The objective of this study was to develop PBPK models that incorporate the haemodynamic changes in hepatic and renal blood flows occurring in chronic heart failure (CHF) and to evaluate these changes in adults and children, using carvedilol as a model drug.MethodsAfter a comprehensive literature search to select the model input parameters, two PBPK models were developed. Model 1 was based on human liver and intestinal microsome clearances, and model 2 was based on clearance by specific cytochrome P450 enzymes. After evaluation of both models in healthy adults, the reduced hepatic and renal blood flows were incorporated into the developed models to predict carvedilol exposure in the adult CHF population. The adult carvedilol models were scaled down to children by using Simcyp® (Simcyp Ltd, Sheffield, UK). In order to show the impact of reduced organ blood flows on carvedilol disposition, the predictions in the CHF population were made with and without reductions in organ blood flows.ResultsThe predictions made by both models in healthy adults were comparable and within the 2-fold error range. In adults with CHF, the mean observed/predicted ratio [ratio(Obs/Pred)] for oral clearance (CL/F) without reductions in organ blood flows was outside the 2-fold error range, i.e. 0.34 (95 % confidence interval [CI] 0.31–0.37), with use of both models. The mean CL/F ratio(Obs/Pred) values after incorporation of reduced organ blood flows were 1.0 (95 % CI 0.92–1.08) and 0.95 (95 % CI 0.88–1.03) with use of models 1 and 2, respectively. The mean ratio(Obs/Pred) values for the pharmacokinetic parameters were not improved after incorporation of reduced blood flows in paediatric patients, except in those above 17 years of age, who were categorized according to the New York Heart Association classification of CHF, where the CL/F ratio(Obs/Pred) values in two patients were closer to unity.ConclusionThere was a strong connection between a decrease in hepatic clearance of carvedilol and an increase in the severity of CHF, especially in adults and in paediatric patients above 17 years of age. The incorporated reductions in hepatic and renal blood flows occurring in moderate and severe CHF patients resulted in improved predictions of carvedilol exposure. The developed models can be extended to predict exposures of drugs with high hepatic extraction in the CHF population.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-015-0253-7) contains supplementary material, which is available to authorized users.