Clinical Course Of Heart Failure Research Articles

Low-intensity inflammation as a manifestation of comorbidity and a factor in the unfavorable clinical course of heart failure with preserved ejection fraction

Aim. To analyze the prognostic significance of clinical, anamnestic and paraclinical parameters in patients with heart failure with preserved ejection fraction (HFpEF) and non-obstructive coronary artery disease.Material and methods. The study included 54 patients. Cardiac and lung ultrasound was performed. In addition, the level of N-terminal pro-brain natriuretic peptide (NT-proBNP), interleukin-1β, interleukin-18, growth differentiation factor 15 (GDF-15), and cryopyrin was determined. The level of quality of life, anxiety and depression, and adherence to treatment were analyzed.Results. The patients were divided into 2 following groups: group 1 (n=22) with an unfavorable course and group 2 (n=32) with a favorable disease course. Basic echocardiographic parameters, as well as the number of B-lines in lungs, were comparable in both groups. An unfavorable HFpEF course was associated with a longer history of hypertension — 17,5 [10;20] and 7 [5;15] years (p=0,03), smoking — 36,4 and 9,4% (p=0,035), impaired carbohydrate metabolism — 54,5 and 15,6% (p=0,003) and lower adherence to treatment (p=0,02). In group 1, GDF-15 levels were higher than in group 2 — 1841 [1237;3552] vs 1709,5 [1158;2492] pg/ml (p=0,026).Conclusion. Low-intensity subclinical inflammation, the predisposing factors of which are smoking, impaired carbohydrate metabolism, and a long history of hypertension, is associated with higher GDF-15 values in patients with HFpEF and, along with low patient adherence to treatment, has an adverse effect on the clinical course of heart failure.

CircRNA Larp4b/miR-298-5p/Mef2c Regulates Cardiac Hypertrophy Induced by Angiotensin II.

Cardiac hypertrophy (CH) is an early marker in the clinical course of heart failure. Circular RNAs (circRNAs) play important roles in human disease. However, the role of circ_Larp4b in myocardial hypertrophy has not been studied. Angiotensin II (Ang II) treated HL-1 cells to induce a CH cell model. Quantitative real-time polymerase chain reaction was used to detect the expression of circ_Larp4b, microRNA-298-5p, and myocyte enhancer factor 2 (Mef2c). Western blot detected the protein level of alpha-actinin-2 (ACTN2), beta-myosin heavy chain (β-MHC), atrial natriuretic peptide (ANP), and Mef2c. The relationship between miR-298-5p and circ_Larp4b or Mef2c was verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_Larp4b and Mef2c were upregulated in HL-1 cells treated with Ang II. Moreover, circ_Larp4b down-regulation regulated the progress of CH induced by Ang II. MiR-298-5p was a target of circ_Larp4b, and Mef2c was a target of miR-298-5p. Overexpressed Mef2c reversed the cell size inhibited by miR-298-5p in Ang II-induced HL-1 cells. Circ_Larp4b regulated CH progress by regulating miR-298-5p/Mef2c axis.

Abstract 12486: Predictive Value of Chronotropic Incompetence for Clinical Outcomes in Heart Failure: Findings From the MyoVasc Study

Introduction: Chronotropic incompetence (CI), an important aspect of exercise intolerance, is related to adverse clinical outcomes in heart failure (HF). However, the lack of standardized evaluation of CI results in inconsistent evidence. Aim: To evaluate CI with regard to clinical and medical determinants and relationship to clinical outcomes in HF. Methods: Data from the MyoVasc study (NCT04064450), a prospective cohort on HF, were analyzed. Subjects underwent deep clinical phenotyping, including cardiopulmonary exercise testing on a cycle ergometer. Measures of CI were evaluated, with continuous predicted heart rate reserve (pHRR) emerging as the most clinically relevant definition for operationalizing CI. Clinical and medical determinants of CI were assessed in multivariable linear regression models and outcomes in Cox regression models. Results: The analysis sample included 886 subjects (median age 63 years [interquartile range (IQR) 55; 72]; 29.9% women) who achieved maximal exertion (respiratory exchange ratio>1.0). Symptomatic HF stage C/D was present in 42.8% (379) of the subjects. Sixteen drug groups were identified as CI modulators including β-blockers (β-estimate per SD -0.83 [95% confidence interval -0.95;-0.70], p<0.0001) and antiarrhythmics (β SD -0.93 [-1.30;-0.56], p<0.0001). New York Heart Association functional class, smoking, fatty liver index (FLI), and diabetes mellitus (DM) were the strongest determinants of CI in all subjects independently of sex, age, and previously identified medication. Determinants differed according to left ventricular ejection fraction [LVEF] (≥50 vs <50%), being strongly associated with markers of HF (NT-proBNP) and lung function (FEV1) in HF with reduced EF and more linked to DM or the FLI in HF with preserved EF. In Cox regression analysis adjusted for clinical profile, pHRR independently predicted all-cause death (HR SD 1.86 [1.41;2.45], p<0.0001) and worsening of HF (HR SD 1.37 [1.04;1.81], p=0.025). Conclusions: CI strongly predicted clinical outcomes and revealed relevant differences between HF with preserved and reduced EF. This highlights the relevance of impaired response to exercise in the clinical course of HF with implication for risk stratification and intervention.

Clinical use of voice measurement in patients with heart failure: study protocol

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Chronic conditions are the main causes of morbidity and mortality worldwide. Heart failure (HF) has a prevalence between 0.5% and 2% in the western population and the number is destined to increase from 25% in 2012 to 46% in 2030. Older adults affected by HF have difficulties to recognize signs and symptoms of the disease, bringing to a reduction of life expectancy. The voice is a complex coordination mechanism between systems and subsystems (i.e. glottis, lung, nose,..). Changes in voice parameters, measuring by algorisms of artificial intelligence, could be useful markers of HF exacerbation. To date, no prior studies have investigated the changing of voice parameters in HF patients and the relationships between voice parameter changes and the clinical course of HF. Aims Explore voice parameter differences between HF patients and healthy subjects; to investigate the relationships between voice parameter changes and the clinical course of the disease. Methods Observational study. Patients with HF and healthy subjects between 60 to 80 y/o will be enrolled in inpatient and outpatient settings. Patients and healthy participants will record voices by microphones and smartphones. Voice data will be analyzed with algorithms of artificial intelligence. Results This study will identify differences in voice parameters between HF patients and healthy participants, and the associations between the voice parameters and the clinical changes of HF patients. Conclusion Monitoring of voice parameters allows to clinicians to early identify, via voice changes, signs and symptoms of HF exacerbations, and to monitor patients at home.

Critical Analysis of the Effects of SGLT2 Inhibitors on Renal Tubular Sodium, Water and Chloride Homeostasis and Their Role in Influencing Heart Failure Outcomes.

SGLT2 (sodium-glucose cotransporter 2) inhibitors interfere with the reabsorption of glucose and sodium in the early proximal renal tubule, but the magnitude and duration of any ensuing natriuretic or diuretic effect are the result of an interplay between the degree of upregulation of SGLT2 and sodium-hydrogen exchanger 3, the extent to which downstream compensatory tubular mechanisms are activated, and (potentially) the volume set point in individual patients. A comprehensive review and synthesis of available studies reveals several renal response patterns with substantial variation across studies and clinical settings. However, the common observation is an absence of a large acute or chronic diuresis or natriuresis with these agents, either when given alone or combined with other diuretics. This limited response results from the fact that renal compensation to these drugs is rapid and nearly complete within a few days or weeks, preventing progressive volume losses. Nevertheless, the finding that fractional excretion of glucose and lithium (the latter being a marker of proximal sodium reabsorption) persists during long-term treatment with SGLT2 inhibitors indicates that pharmacological tolerance to the effects of these drugs at the level of the proximal tubule does not meaningfully occur. This persistent proximal tubular effect of SGLT2 inhibitors can be hypothesized to produce a durable improvement in the internal set point for volume homeostasis, which may become clinically important during times of fluid expansion. However, it is difficult to know whether a treatment-related change in the volume set point actually occurs or contributes to the effect of these drugs to reduce the risk of major heart failure events. SGLT2 inhibitors exert cardioprotective effects by a direct effect on cardiomyocytes that is independent of the presence of or binding to SGLT2 or the actions of these drugs on the proximal renal tubule. Nevertheless, changes in the volume set point mediated by SGLT2 inhibitors might potentially act cooperatively with the direct favorable molecular and cellular effects of these drugs on cardiomyocytes to mediate their benefits on the development and clinical course of heart failure.

Parkia speciosa Hassk. Empty Pod Extract Prevents Cardiomyocyte Hypertrophy by Inhibiting MAPK and Calcineurin-NFATC3 Signaling Pathways.

Cardiac hypertrophy is an early hallmark during the clinical course of heart failure. Therapeutic strategies aiming to alleviate cardiac hypertrophy via the mitogen-activated protein kinase (MAPK)/calcineurin-nuclear factor of activated T-cells (NFAT) signaling pathway may help prevent cardiac dysfunction. Previously, empty pod ethanol crude extract of Parkia speciosa Hassk was shown to demonstrate protective effects against cardiomyocyte hypertrophy. Therefore, the current study aimed to investigate the effects of various fractions of the plant ethanol extract on the MAPK/NFAT signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Simultaneous treatment with ethyl acetate (EA) fraction produced the most potent antihypertrophic effect evidenced by the reduced release of B-type natriuretic peptide (BNP). Subsequently, treatment with the EA fraction (6.25, 12.5, and 25 μg/mL) prevented an Ang II-induced increase in cell surface area, hypertrophic factors (atrial natriuretic peptide and BNP), reactive oxygen species, protein content, and NADPH oxidase 4 expression in the cells. Furthermore, EA treatment attenuated the activation of the MAPK pathway and calcineurin-related pathway (GATA-binding protein 4 and NFATC3), which was similar to the effects of valsartan (positive control). Our findings indicate that the EA fraction prevents Ang II-induced cardiac hypertrophy by regulating the MAPK/calcineurin-NFAT signaling pathway.

Riociguat in pulmonary hypertension and heart failure with preserved ejection fraction: the haemoDYNAMIC trial.

AimsThe presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF.Methods and ResultsThe phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicentre DYNAMIC trial assessed riociguat in PH-HFpEF. Patients were recruited at five hospitals across Austria and Germany. Key eligibility criteria were mean pulmonary artery pressure ≥25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction ≥50%. Patients were randomized to oral treatment with riociguat or placebo (1:1). Patients started at 0.5 mg three times daily (TID) and were up-titrated to 1.5 mg TID. The primary efficacy endpoint was change from baseline to week 26 in cardiac output (CO) at rest, measured by right heart catheterization. Primary efficacy analyses were performed on the full analysis set. Fifty-eight patients received riociguat and 56 patients placebo. After 26 weeks, CO increased by 0.37 ± 1.263 L/min in the riociguat group and decreased by −0.11 ± 0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval 0.112, 0.971; P = 0.0142). Five patients dropped out due to riociguat-related adverse events but no riociguat-related serious adverse event or death occurred.ConclusionThe vasodilator riociguat improved haemodynamics in PH-HFpEF. Riociguat was safe in most patients but led to more dropouts as compared to placebo and did not change clinical symptoms within the study period.

Prognostic value of hypoxia-inducible factor-1 alpha gene polymorphism in patients with heart failure with preserved ejection fraction and obstructive sleep apnea

Aim. To study the associations of hypoxia-inducible factor-1 alpha (HIF-1α) gene polymorphism (rs11549465) with the clinical course of heart failure (HF) with reserved ejection fraction (HFpEF) in patients with obesity and moderate and severe obstructive sleep apnea (OSA).Material and methods. The study included 76 men with HFpEF and OSAS. Patients underwent a polysomnography, echocardiography, and a 6-minute walk test. In addition, apnea/hypopnea index was calculated, and the level of N-terminal pro-brain natriuretic peptide (NT-proBNP) was assessed. HIF1A gene polymorphisms (rs11549465) were analyzed using polymerase chain reaction. After 12-month follow-up, the clinical course of HF was assessed.Results. The T/T genotype of the HIF1A gene was associated with a high risk of HF progression (p=0,004), development of supraventricular premature beats (p=0,004) and atrial fibrillation (p=0,039). Carrying the T/T genotype was associated with severe OSA (p=0,006) and increased NT-proBNP (p=0,044), and also correlated with certain echocardiographic characteristics of myocardial remodeling.Conclusion. T/T genotype of the HIF1A gene is associated with OSA severity and increased NT-proBNP, as well as with the severity of left and right heart remodeling. The carriage of this genotype was associated with an unfavorable course of HF and an increased risk of atrial fibrillation in patients with HFpEF and OSA.

Left atrial disease and left atrial reverse remodelling across different stages of heart failure development and progression: a new target for prevention and treatment.

The left atrium is a dynamic chamber with peculiar characteristics. Stressors and disease mechanisms may deeply modify its structure and function, leading to left atrial remodelling and disease. Left atrial disease is a predictor of poor outcomes. It may be a consequence of left ventricular systolic and diastolic dysfunction and neurohormonal and inflammatory activation and/or actively contribute to the progression and clinical course of heart failure through multiple mechanisms such as left ventricular filling and development of atrial fibrillation and subsequent embolic events. There is growing evidence that therapy may improve left atrial function and reverse left atrial remodelling. Whether this translates into changes in patient's prognosis is still unknown.In this review we report current data about changes in left atrial size and function across different stages of development and progression of heart failure. At each stage, drug therapies, lifestyle interventions and procedures have been associated with improvement in left atrial structure and function, namely a reduction in left atrial volume and/or an improvement in left atrial strain function, a process that can be defined as left atrial reverse remodelling and, in some cases, this has been associated with improvement in clinical outcomes. Further evidence is still needed mainly with respect of the possible role of left atrial reverse remodelling as an independent mechanism affecting the patient's clinical course and as regards better standardization of clinically meaningful changes in left atrial measurements. Summarizing current evidence, this review may be the basis for further studies.

Elevated levels of apelin predict favorable clinical course of heart failure in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Apelin is a regulatory peptide having positive inotrope and reparative abilities. Type 2 diabetes mellitus (T2DM) is common comorbidity that is associated to occurrence of HF mainly HF with preserved ejection fraction (HFpEF). The discriminative potency of conventional cardiac biomarkers such as natriuretic peptides in HFpEF was found to be sufficiently lower compared to HF with reduced / mildly reduced ejection fraction (HFrEF / HFmrEF). The aim of the study was to investigate whether serum levels of apelin predict HF in patients with T2DM. Methods A total of 108 HF patients (left ventricular ejection fraction [LVEF] <60%) with T2DM were prospectively involved in the study. Entire HF population consisted of 58 HFpEF patients and 50 HFmrEF / HFrEF aged from 41 to 62 years. Cardiac hemodynamic performances were obtained by B-mode echocardiography, Doppler and TDI. The levels of apelin, N-terminal pro-brain natriuretic peptide (NT-proBNP), high sensitive troponin T (hs-TnT) were measured by ELISA. Combined end-point for the study were defined as all-cause death and any non-fatal cardiovascular event or HF hospitalization during 52 weeks. Results The combined end-point occurred in 37 patients (34.3%) from entire population. The levels of apelin in patients who had the combined end-point were significantly lower (3.55 ng/mL, 95% confidence interval [CI]=3.12-3.95 ng/mL) compared with those who did not meet it (5.60 ng/mL; 95% CI = 4.10-7.10 ng/mL; P=0.001). ROC curve revealed that the best-balanced cut-off point for apelin levels, which predicted combined end-point occurrence, was 3.88 ng/mL (AUC=0.82; P=0.001). Cox regression showed that apelin levels > 3.55 ng/mL (Odds Ratio [OR]= 2.02; 95% CI=1.14-3.25; P=0.001), LVEF< 49% (OR=1.48; 95% CI=1.22-1.68, P = 0.001), NT-proBNP > 785 ng/mL (OR =2.08; 95% CI = 1.03–4.12; P = 0.001), global longitudinal strain < -8.6% (OR =2.02; 95% CI = 1.09–3.10; P = 0.001), hs-TnT > 0.4 ng/mL (OR=1.98; 95% CI=1.10-2.93; P=0.001), estimated glomerular filtration rate <60 mL/min/1.73 m2 (OR=1.46; 95% CI=1.09-2.55; P=0.001) and history of atrial fibrillation (OR=1.14; 95% CI=1.02-1.80; P=0.001) predicted the combined end-point. After adjustment for HFpEF, apelin levels > 3.55 ng/mL (OR=2.03; 95% CI=1.10-3.20; P=0.001) and NT-proBNP > 785 ng/mL (OR =2.10; 95% CI = 1.05–3.80; P = 0.001) remain independent predictors for the combined end-point. The addition of apelin to the ABC model (NT-proBNP > 785 ng/mL) improved the relative integrated discrimination indices by 10.5% and net-reclassification improvement for 11.5% for combined end-point. Kaplan – Meier curve showed that patients having the levels of apelin >3.55 ng/mL demonstrated better clinical course of HF compared with those who had lower apelin levels (log rank test p=0.001). In conclusion: We found that apelin levels >3.55 ng/mL regardless of NT-proBNP had positive discriminative ability for clinical course of HF in T2DM patients.

Effects of Metformin in Heart Failure: From Pathophysiological Rationale to Clinical Evidence.

Type 2 diabetes mellitus (T2DM) is a worldwide major health burden and heart failure (HF) is the most common cardiovascular (CV) complication in affected patients. Therefore, identifying the best pharmacological approach for glycemic control, which is also useful to prevent and ameliorate the prognosis of HF, represents a crucial issue. Currently, the choice is between the new drugs sodium/glucose co-transporter 2 inhibitors that have consistently shown in large CV outcome trials (CVOTs) to reduce the risk of HF-related outcomes in T2DM, and metformin, an old medicament that might end up relegated to the background while exerting interesting protective effects on multiple organs among which include heart failure. When compared with other antihyperglycemic medications, metformin has been demonstrated to be safe and to lower morbidity and mortality for HF, even if these results are difficult to interpret as they emerged mainly from observational studies. Meta-analyses of randomized controlled clinical trials have not produced positive results on the risk or clinical course of HF and sadly, large CV outcome trials are lacking. The point of force of metformin with respect to new diabetic drugs is the amount of data from experimental investigations that, for more than twenty years, still continues to provide mechanistic explanations of the several favorable actions in heart failure such as, the improvement of the myocardial energy metabolic status by modulation of glucose and lipid metabolism, the attenuation of oxidative stress and inflammation, and the inhibition of myocardial cell apoptosis, leading to reduced cardiac remodeling and preserved left ventricular function. In the hope that specific large-scale trials will be carried out to definitively establish the metformin benefit in terms of HF failure outcomes, we reviewed the literature in this field, summarizing the available evidence from experimental and clinical studies reporting on effects in heart metabolism, function, and structure, and the prominent pathophysiological mechanisms involved.

Abstract 10837: Prognostic Importance of Atrial Fibrillation in Heart Failure According to Time Elapsed Since Diagnosis

Introduction: Mortality rates in heart failure (HF) are greatest early after onset and decline rapidly with time (with the survival of the less sick patients). However, it is not known if the presence of atrial fibrillation (AF), a well-known risk factor for mortality in this population, alters such course. Methods: From the Danish nationwide administrative database, all first time HF patients were identified between 1998-2018 using ICD coding and followed for all cause mortality until the end of 2018. AF was categorized as occurring antecedent (before), concomitant (with), or after HF diagnosis. Time-dependent Poisson regression model was used to determine mortality rate ratios, using ‘no AF’ as referent, with multivariable adjustment. Results: A total of 252,988 HF patients (45% women, mean age 74 ±13 years) were included. Of these, 54,064 (21%) had AF before HF onset and 27,651 (11%) patients had AF diagnosed concomitantly with HF. During follow-up, 30,565 additional patients developed AF. The cumulative mortality and mortality rates were highest early after onset for all groups, but greater for those with AF versus without AF, regardless of the time of onset, Figure A and B. Of note, the rates declined substantially more and faster for patients without AF, rendering AF greater prognostic importance the longer out from initial diagnosis, p for interaction between AF groups and HF duration <0.0001, Figure C. Conclusion: While mortality declined in all patients with HF over time, patients with AF experienced substantially less decline in mortality than the no AF group, rendering AF of greater prognostic importance later in the clinical course of HF.

Acute Decompensated Heart Failure (ADHF) with aortic dissection Stanford A in middle aged man: a case report

Background: Heart failure is a clinical syndrome with shortness of breath, fluid retention, and the heart's structural and functional disorder. Each year, there were 7,2 cases every 1000 people on male and 4,7 cases every 1000 people on the female. Aortic dissection is an emergency disease in which the symptoms are similar to ischemic heart disease, that 38% of patients got misdiagnosed on the first evaluations. Because of the clinical course of heart failure and misdiagnosed aortic dissection that frequently happened, authors are interested in making a case report with both conditions.Case report: A male patient, 39 years old, complained of shortness of breath and epigastrium pain. The patient was diagnosed with Acute Decompensated Heart Failure (ADHF) profile B with emergency hypertension and suspected aortic dissection based on history and physical examination. The patient was also diagnosed with acute kidney injury stage 1. CT angiography showed widening of the aorta ascending until arcus aorta with a Stanford type A aortic dissection diagnosis.Conclusion: The condition of aortic dissection can coincide with acute heart failure. Therefore, a clinician must be aware of the emergency of dissection and know the initial symptoms of dissection. The typical clinical symptoms of dissection lead us to perform imaging studies that ultimately lead to a thoracoabdominal CTA to diagnose the dissection.

Social and environmental risks as contributors to the clinical course of heart failure.

Heart failure is a major contributor to healthcare expenditures. Many clinical risk factors for the development and exacerbation of heart failure had been reported, including diabetes, renal dysfunction, and respiratory disease. In addition to these clinical parameters, the effects of social factors, such as occupation or lifestyle, and environmental factors may have a great impact on disease development and progression of heart failure. However, the current understanding of social and environmental factors as contributors to the clinical course of heart failure is insufficient. To present the knowledge of these factors to date, this comprehensive review of the literature sought to identify the major contributors to heart failure within this context. Social factors for the risk of heart failure included occupation and lifestyle, specifically in terms of the effects of specific occupations, occupational exposure to toxicities, work style, and sleep deprivation. Socioeconomic factors focused on income and education level, social status, the neighborhood environment, and marital status. Environmental factors included traffic and noise, air pollution, and other climate factors. In addition, psychological stress and behavior traits were investigated. The development of heart failure may be closely related to these factors; therefore, these data should be summarized for the context to improve their effects on patients with heart failure. The present study reviews the literature to summarize these influences.

Effect of atorvastatin on the lipid profile, markers of immune inflammation and symptomatic severity of heart failure in patients with myocarditis

Abstract. The effect of atorvastatin on the immune system and lipid metabolism after 24-week treatment of patients with chronic myocarditis is considered. Statins have been found to improve the clinical course of heart failure with a preserved ejection fraction in patients with myocarditis: they reduce the functional class of heart failure, improve the systolic function of the heart and its arrhythmogenic potential. Despite the large amount of conflicting data in the field of statin use in heart failure, one can think about the possible influence of molecular differences in statins on their pharmacological and pleiotropic effects. In particular, atorvastatin, which has lipophilic properties, is able to penetrate cardiomyocytes in contrast to hydrophilic rosuvastatin, which may partially explain the positive cardiac effects of atorvastatin in patients with heart failure with a preserved ejection fraction. The probable basis for the positive effect of atorvastatin on morphofunctional parameters in heart failure is its positive pleiotropic effects associated with a decrease in рro-inflammatory immune markers and subsequent leveling of negative neurohumoral activation. An additional mechanism that caused the positive effect of atorvastatin on the clinical course of heart failure can be considered a factor of preservation of systolic function of the left ventricle.

Heart failure documentation in outpatients with diabetes and volume overload: an observational cohort study from the Diabetes Collaborative Registry

BackgroundHeart failure is a common and devastating complication of type 2 diabetes (T2D). Prompt recognition of heart failure may avert hospitalization, facilitate use of guideline-directed therapies, and impact choice of T2D medications. We sought to determine the rate and factors associated with heart failure documentation in T2D patients with evidence of volume overload requiring loop diuretics.MethodsDCR is an on-going, prospective US registry of outpatient T2D patients from > 5000 cardiology, endocrinology, and primary care clinicians (current analysis used data from 2013–2019). Among T2D patients receiving loop diuretics, we examined the rate of chart documentation of heart failure. We used a 3-level hierarchical logistic regression model (patients nested within physician within practice) to examine factors associated with heart failure diagnosis.ResultsAmong 1,322,640 adults with T2D, 225,125 (17.0%) were receiving a loop diuretic, of whom 91,969 (40.9%) had documentation of heart failure. Male sex, lower body mass index, atrial fibrillation, chronic kidney disease, and coronary artery disease were associated with greater odds of heart failure diagnosis. After accounting for patient factors, patients seen by cardiologists were the most likely to have HF documented followed by PCPs and then endocrinologists.ConclusionsAmong US outpatients with T2D, 17% of patients had evidence of volume overload—defined by loop diuretic prescription—of whom fewer than half had a clinical diagnosis of heart failure. While there may be non-heart failure indications for loop diuretics, our data suggest that a substantial proportion of T2D patients may have unrecognized heart failure and therefore could be missing opportunities for targeted therapies that could alter the clinical course of heart failure.

<p>A Novel Radiofrequency Device to Monitor Changes in Pulmonary Fluid in Dialysis Patients</p>

Background and ObjectivesFluid monitoring is an important management strategy in patients with chronic kidney disease (CKD) and heart failure (HF). The µCor™ Heart Failure and Arrhythmia Management System uses a radiofrequency-based thoracic fluid index (TFI) to track pulmonary edema. During hemodialysis, the acute removal of fluid through ultrafiltration offers a model for measuring a patient’s fluid status. The objective of the study was to assess the relationship between the device measured TFI and ultrafiltration volume (UFV).Design, Setting, Participants, and MeasurementsPatients undergoing chronic dialysis with and without heart failure were enrolled in the study. The relationship between TFI and UFV in each individual subject was assessed by calculating the Pearson correlation coefficient (r). The average correlation across all subjects was calculated through the use of the Fisher’s z transform. Responder analysis was performed to assess the magnitude of change in TFI before and after dialysis.ResultsTwenty subjects were enrolled in the trial. The mean volume of fluid removal was 3.63 L (SD 0.88 L). The mean correlation based on Fisher’s transform was 0.95 CI (0.92–0.99). Responder analysis showed that the mean reduction of TFI after dialysis was 5.5% ± 3.8.ConclusionThe µCor system provides radiofrequency-based measurements of thoracic fluid which correlate well with total body fluid removal in a real-world setting. Fluid management based on the radar-derived TFI may provide benefits to dialysis patients and serves as a potential model for pulmonary edema common to the clinical course of heart failure.

Effects of spironolactone and eplerenone on left ventricular diastolic function and neurohumoral factors in patients with heart failure

Aim. To study the effects  of spironolactone  and eplerenone on left ventricular diastolic function and neurohumoral factors in patients with heart failure (HF).Material and methods. We examined 131 patients  with coronary artery disease  and NYHA class  I-III HF. Patients  were randomized  into groups depending  on HF class: class I (n=31), class II (n=51) and class III (n=49).Results. The study revealed that the clinical course  of HF and LV diastolic dysfunction are associated with an increased  level of neurohormones  and are characterized by significantly high levels of aldosterone  and norepinephrine  in patients  with a restrictiveLV diastolic dysfunction. A correlation was found between  the level of neurohormones  (aldosterone  and norepinephrine)  and heart  remodeling parameters:  an inverse correlation with an ejection fraction (r=-0,68, r=-0,61,  respectively) and a direct correlation with LV  end-diastolic volume (r=0,58, r=0,66, respectively). Long-term treatment  with spironolactone  and eplerenone had a positive effect, reducing the level of mentioned neurohormones. In patients with class II HF, both drugs had a positive effect on the level of aldosterone  and norepinephrine, reducing them by 26,6% and 20,2% in the spironolactone  group and by 28,4% and  24,6% in the eplerenone group,  respectively.  In patients with class  III  HF, the decrease in aldosterone  level was more pronounced  in those taking eplerenone than spironolactone:  32,1% vs 20,2%, respectively.Conclusion. In patients  with HF, combination therapy with the inclusion of spironolactone  significantly reduced  the level of neurohormones mainly in patients with class II HF and, to a lesser extent, in those with class III HF. This suggests that combination therapy with spironolactone is less effective than with eplerenone in relation to neurohormones’  levels. 

Cost-Effectiveness of the International Late Effects of Childhood Cancer Guideline Harmonization Group Screening Guidelines to Prevent Heart Failure in Survivors of Childhood Cancer.

Survivors of childhood cancer treated with anthracyclines and/or chest-directed radiation are at increased risk for heart failure (HF). The International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms, but evidence supporting its frequency and cost-effectiveness is limited. Using the Childhood Cancer Survivor Study and St Jude Lifetime Cohort, we developed a microsimulation model of the clinical course of HF. We estimated long-term health outcomes and economic impact of screening according to IGHG-defined risk groups (low [doxorubicin-equivalent anthracycline dose of 1-99 mg/m2 and/or radiotherapy < 15 Gy], moderate [100 to < 250 mg/m2 or 15 to < 35 Gy], or high [≥ 250 mg/m2 or ≥ 35 Gy or both ≥ 100 mg/m2 and ≥ 15 Gy]). We compared 1-, 2-, 5-, and 10-year interval-based screening with no screening. Screening performance and treatment effectiveness were estimated based on published studies. Costs and quality-of-life weights were based on national averages and published reports. Outcomes included lifetime HF risk, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs < $100,000 per QALY gained were considered cost-effective. Among the IGHG risk groups, cumulative lifetime risks of HF without screening were 36.7% (high risk), 24.7% (moderate risk), and 16.9% (low risk). Routine screening reduced this risk by 4% to 11%, depending on frequency. Screening every 2, 5, and 10 years was cost-effective for high-risk survivors, and every 5 and 10 years for moderate-risk survivors. In contrast, ICERs were > $175,000 per QALY gained for all strategies for low-risk survivors, representing approximately 40% of those for whom screening is currently recommended. Our findings suggest that refinement of recommended screening strategies for IGHG high- and low-risk survivors is needed, including careful reconsideration of discontinuing asymptomatic left ventricular dysfunction and HF screening in low-risk survivors.

Clinical course after a first episode of heart failure: insights from the Framingham Heart Study.

We sought to describe the frequency, type and timing of clinical events, and delineate patterns in their transitions, after a first episode of heart failure (HF). In 1036 Framingham participants with new-onset HF (mean age 79 years; 53% women), we used mixture models to estimate probabilities of, and time to cardiac death, other cardiovascular disease (CVD) death, recurrent HF, cardiac events and other CVD events, accounting for age, sex, HF type (preserved vs. reduced ejection fraction), and prevalent cardiac/CVD events. The most common first events after new-onset HF were cardiac (36%), recurrent HF (28%) and death (29%). Compared with recurrent HF (referent transition state), prevalent cardiac events were associated with higher odds of fatal [odds ratio (OR) 1.90, 95% confidence interval (CI) 1.11-3.23] and non-fatal (OR 2.13, 95% CI 1.52-3.00) cardiac events; prevalent CVD increased odds of other CVD death (OR 1.90, 95% CI 1.04-3.47). Among 715 participants without a fatal initial event, there were 3337 distinct epochs (inter-event time periods), with median 3.0 epochs/participant [49% cardiac (n=1639); 27% recurrent HF (n=912)]. Median inter-event times varied between 12 to 285 days (recurrent HF to other CVD death and non-fatal other CVD, respectively). Prior HF, cardiac and other CVD events significantly increased odds of developing the same event-type (OR ∼ 5-7-fold), with shortened time to recurrence, indicating 'rapid cycling loops' of the same event type. HF type did not impact the nature or timing of future events. Comorbidities but not HF type impact clinical course of HF by influencing the type and timing of subsequent events, denoting 'natural history loops' within the overall HF population.