Early Stages Of Heart Failure Research Articles

Non-linear causal effects of kidney function on the risk of heart failure: a Mendelian randomization study

Abstract Background Kidney insufficiency is defined as the early stage of heart failure, but Mendelian randomization (MR) analyses based on several large heart failure cohorts suggest no linear causal effect between kidney function and heart failure (HF), inconsistent with observational studies evidence. However, whether there is a non-linear causal relationship between kidney function and HF has not been reported. Methods and Results Observational and non-linear MR analyses were performed using individual-level data from a UK Biobank cohort of white British ancestry subjects (N = 386,304). There were non-linear observational associations of between kidney function as assessed with estimated glomerular filtration rate (eGFR) and HF (P for nonlinear <0.001). Non-linear MR analyses showed a U-shaped association between genetically predicted eGFR values (both creatinine- and cystatin C-based eGFR) and the risk of HF (Quadratic P value < 0.05) and the risk of HF increased with both reduced and supranormal eGFR levels (β1 = -1.70E-05, P1-value = 0.004; β2 = 3.56E-06, P2-value = 0.004). Conclusion This study observed a non-linear U-shaped genetic relationship between eGFR and HF outcomes, indicating that both reduced and supranormal eGFR may be causally linked to a higher risk of HF.Central Illustration

Cardiac power output associated with hospitalization and mortality in coronary artery disease patients at stage B heart failure

BackgroundCardiac power output (CPO) predicts outcomes in advanced heart failure (HF) and cardiogenic shock, but its role in early HF stages is unclear. This study assessed the prognostic value of CPO in coronary artery disease patients with asymptomatic left ventricular systolic dysfunction (ALVSD) at stage B HF. MethodsWe conducted a retrospective analysis of coronary artery disease patients who underwent coronary and pulmonary artery catheterization between 2006 and 2016. Stage B HF with ALVSD was defined as left ventricular ejection fraction < 50 %, without HF symptoms, signs, or prior HF hospitalization. CPO was derived from invasive hemodynamic parameters. Endpoints included HF hospitalization, cardiovascular mortality, and all-cause mortality over a 5-year follow-up. ResultsA total of 783 coronary artery disease patients with ALVSD at stage B HF were enrolled. Incidence rates (per 1000 person-years) were 13.9 for HF hospitalization, 14.5 for cardiovascular mortality, and 23.7 for all-cause mortality.Multivariate analysis adjusting for covariates demonstrated that CPO was independent associated with all endpoints. Patients with a low CPO (<0.97 Watts) were at significantly higher risk for HF hospitalization (adjusted hazard ratio [HR]: 4.04; 95 % CI: 1.53 – 10.6; p = 0.005), cardiovascular mortality (adjusted HR: 2.73; 95 % CI: 1.19 – 6.27; p = 0.018), and all-cause mortality (adjusted HR: 1.86; 95 % CI: 1.05 – 3.30; p = 0.035) compared to those with higher CPO, regardless of subgroup classification. ConclusionResting CPO in patients with ALVSD is significantly associated with adverse events, including HF hospitalization and mortality, highlighting its value in early-stage HF management.

CircRNA Interference Pathway: A New Target for Intervention in Different Stages of Heart Failure.

Cardio-cerebrovascular disease has seen a rapid rise in recent years, with Heart Failure (HF) - a terminal stage of various cardiovascular diseases - also on the rise. HF has a complex pathogenesis involving multiple factors, such as inflammation, fibrosis, and oxidative stress. Due to its unique reverse shear mechanism, HF exhibits distinct expression patterns across different diseases. CircRNA has been linked to conditions like cancer, diabetes, and osteoarthritis. This article briefly introduces the mechanisms of circRNA biogenesis and its associated biological functions, focusing on CircSLC8A1-1, CircRNA_000203, and others at the early stage of HF, CircRNA PAN3, CircRNA (ACR), and others during the progression of HF, and CircHIPK3, CircNfix, and others at the end stage of HF. These circRNAs play a participatory role in the exact mechanism. As a research method, circRNA can be utilized to study the pathogenesis of heart failure and serve as a target for drug discovery and development. Therefore, circRNA's ability to mark the disease at different stages has significant guiding implications for HF monitoring, treatment, and prognosis.

#2616 AVF volume blood flow reduction in NYHA III patients—is it too late?

Abstract Background and Aims Heart failure (HF) with preserved / high cardiac output (CO) is a well-known syndrome in patients with high-flow AVF. However, the threshold for classifying an AVF as high-flow is currently undefined. Cardio-fistular recirculation (CFR) is often used as a criterion, with values greater than 25-30% considered cardiotoxic and associated with adverse outcomes. Additionally, CFR is one of the few easily modifiable risk factors through surgical reduction of AVF volume blood flow (Qa). The study aimed to evaluate the extent of involution of heart structural and functional changes following Qa reduction. Method A prospective cohort study included 86 adult HD patients who met the inclusion criteria: HF with preserved / high CO, CFR &amp;gt; 25%, eKt/V &amp;gt; 1.2. Non-inclusion criteria: arrhythmias (except grade I AV block), valvular disease (except mitral regurgitation I-II). Patients were divided into two groups according to the severity of symptoms: NYHA I-II (N = 39) and NYHA III-IV (N = 47). All patients underwent a thorough examination, Qa assessment and ECHO-CG with tissue Doppler on the interdialytic day immediately prior to surgery. Qa reduction was achieved by external PTFE banding, PTFE graft segment placement or aneurysmorrhaphy (in case of coexisting AVF aneurysm). Long-term results were evaluated at 6 months after surgery. As the aim was to evaluate the dynamics, patients who died during follow-up, underwent conversion of KRT, or had a change in vascular access were excluded. Results Table 1 presents the descriptive statistics of the patients prior to surgery. Both groups of patients showed a significant decrease in Qa, CO, cardiac index, end-systolic and end-diastolic volume indices, and LV myocardial mass index, while EF remained unchanged (data not shown). At the same time, there were no significant differences in the dynamics of the above parameters (group*time interaction in the mixed-effects model). Fig. 1 shows that there was a significant group*time interaction: there was a significant difference in CFR before surgery (p = 0.001), but not after (p = 0.958). In both groups, CFR was adjusted to achieve optimal values. The E/A ratio was not different before the surgery (p = 0.209), but it was different after the surgery (p &amp;lt; 0.001). NT-proBNP levels were higher in the NYHA III-IV group both preoperatively (p &amp;lt; 0.001) and postoperatively (p &amp;lt; 0.001). We have observed a similar pattern in the dynamics of the PASP as well (p &amp;lt; 0.001 at both time points). The likelihood of complete weaning from CHF therapy at 6 months after Qa reduction is almost twice as high in the NYHA I-II group (RR = 1.93 [95% CI 1.2; 3.18], p = 0.009). Conclusion Defining AVF as high-flow based solely on Qa value is not accurate. Instead, it is more appropriate to define cardiotoxicity based on both CFR and the severity of clinical symptoms. Patients in NYHA III-IV benefit less from Qa reduction than patients in NYHA I-II and are more likely to retain diastolic dysfunction and pulmonary hypertension. We recommend reducing Qa in the early stages of HF.

Implications and hidden toxicity of cardiometabolic syndrome and early-stage heart failure in carfilzomib-induced cardiotoxicity.

Cancer therapy-related cardiovascular adverse events (CAEs) in presence of comorbidities, are in the spotlight of the cardio-oncology guidelines. Carfilzomib (Cfz), indicated for relapsed/refractory multiple myeloma (MM), presents with serious CAEs. MM is often accompanied with co-existing comorbidities. However, Cfz use in MM patients with cardiometabolic syndrome (CMS) or in heart failure with reduced ejection fraction (HFrEF), is questionable. ApoE-/- and C57BL6/J male mice received 14 weeks Western Diet (WD) (CMS models). C57BL6/J male mice underwent permanent LAD ligation for 14 days (early-stage HFrEF model). CMS- and HFrEF-burdened mice received Cfz for two consecutive or six alternate days. Daily metformin and atorvastatin administrations were performed additionally to Cfz, as prophylactic interventions. Mice underwent echocardiography, while proteasome activity, biochemical and molecular analyses were conducted. CMS did not exacerbate Cfz left ventricular (LV) dysfunction, whereas Cfz led to metabolic complications in both CMS models. Cfz induced autophagy and Ca2+ homeostasis dysregulation, whereas metformin and atorvastatin prevented Cfz-mediated LV dysfunction and molecular deficits in the CMS-burdened myocardium. Early-stage HFrEF led to depressed LV function and increased protein phosphatase 2A (PP2A) activity. Cfz further increased myocardial PP2A activity, inflammation and Ca2+-cycling dysregulation. Metformin co-administration exerted an anti-inflammatory potential on the myocardium without improving LV function. CMS and HFrEF seem to exacerbate Cfz-induced CAEs, by presenting metabolism-related hidden toxicity and PP2A-related cardiac inflammation, respectively. Metformin retains its prophylactic potential in the presence of CMS, while mitigating inflammation and Ca2+ signalling dysregulation in the HFrEF myocardium.

SIRT3 regulates cardiolipin biosynthesis in pressure overload-induced cardiac remodeling by PPARγ-mediated mechanism.

Cardiac remodeling is the primary pathological feature of chronic heart failure (HF). Exploring the characteristics of cardiac remodeling in the very early stages of HF and identifying targets for intervention are essential for discovering novel mechanisms and therapeutic strategies. Silent mating type information regulation 2 homolog 3 (SIRT3), as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolism. However, whether SIRT3 plays a role in cardiac remodeling by regulating the biosynthesis of mitochondrial cardiolipin (CL) is unknown. In this study, we induced pressure overload in wild-type (WT) and SIRT3 knockout (SIRT3-/-) mice via transverse aortic constriction (TAC). Compared with WT mouse hearts, the hearts of SIRT3-/- mice exhibited more-pronounced cardiac remodeling and fibrosis, greater reactive oxygen species (ROS) production, decreased mitochondrial-membrane potential (ΔΨm), and abnormal mitochondrial morphology after TAC. Furthermore, SIRT3 deletion aggravated TAC-induced decrease in total CL content, which might be associated with the downregulation of the CL synthesis related enzymes cardiolipin synthase 1 (CRLS1) and phospholipid-lysophospholipid transacylase (TAFAZZIN). In our in vitro experiments, SIRT3 overexpression prevented angiotensin II (AngII)- induced aberrant mitochondrial function, CL biosynthesis disorder, and peroxisome proliferator-activated receptor gamma (PPARγ) downregulation in cardiomyocytes; meanwhile, SIRT3 knockdown exacerbated these effects. Moreover, the addition of GW9662, a PPARγ antagonist, partially counteracted the beneficial effects of SIRT3 overexpression. In conclusion, SIRT3 regulated PPARγ-mediated CL biosynthesis, maintained the structure and function of mitochondria, and thereby protected the myocardium against cardiac remodeling.

Patient Focus: Moving Beyond Step Count: An Explanation of Real-World Walking Behaviors Are Associated With Early-Stage Heart Failure: A Project Baseline Health Study

In this issue of the Journal of Cardiac Failure, Dr. Sooyoon Shin and colleagues look at whether information from wearable devices, or activity trackers, could improve how a medical team monitors activity limitations for people who are at risk of developing heart failure symptoms.

Real-world walking behaviors are associated with early-stage heart failure: a Project Baseline Health Study

BackgroundData collected via wearables may complement in-clinic assessments to monitor subclinical heart failure (HF). ObjectivesEvaluate the association of sensor-based digital walking measures with HF stage and characterize their correlation with in-clinic measures of physical performance, cardiac function and participant reported outcomes (PROs) in individuals with early HF. MethodsThe analyzable cohort included participants from the Project Baseline Health Study (PBHS) with HF stage 0, A, or B, or adaptive remodeling phenotype (without risk factors but with mild echocardiographic change, termed RF-/ECHO+) (based on available first-visit in-clinic test and echocardiogram results) and with sufficient sensor data. We computed daily values per participant for 18 digital walking measures, comparing HF subgroups vs stage 0 using multinomial logistic regression and characterizing associations with in-clinic measures and PROs with Spearman's correlation coefficients, adjusting all analyses for confounders. ResultsIn the analyzable cohort (N=1265; 50.6% of the PBHS cohort), one standard deviation decreases in 17/18 walking measures were associated with greater likelihood for stage-B HF (multivariable-adjusted odds ratios [ORs] vs stage 0 ranging from 1.18-2.10), or A (ORs vs stage 0, 1.07-1.45), and lower likelihood for RF-/ECHO+ (ORs vs stage 0, 0.80-0.93). Peak 30-minute pace demonstrated the strongest associations with stage B (OR vs stage 0=2.10; 95% CI:1.74-2.53) and A (OR vs stage 0=1.43; 95% CI:1.23-1.66). Decreases in 13/18 measures were associated with greater likelihood for stage-B HF vs stage A. Strength of correlation with physical performance tests, echocardiographic cardiac-remodeling and dysfunction indices and PROs was greatest in stage B, then A, and lowest for 0. ConclusionsDigital measures of walking captured by wearable sensors could complement clinic-based testing to identify and monitor pre-symptomatic HF.

The Role of the Wearable Defibrillator in Heart Failure.

Wearable cardioverter defibrillators (WCDs) have been developed as a temporary measure for protecting patients at risk for sudden cardiac death that do not meet the indication for implantable cardioverter defibrillator (ICD), most notably in the early stages of heart failure with reduced ejection fraction before reassessment of their left ventricular ejection fraction. In this review, we report available evidence in the literature and guidelines regarding WCD use in order to try to define the role WCDs may have in heart failure. In the last decade, most observational studies found WCDs to be both safe and effective in terminating ventricular arrhythmias in various indications, mostly centered around heart failure with reduced ejection fraction. The only available randomized controlled trial using WCD did not however show a benefit on patients' survival. Hence, recent guidelines only recommended its use in limited indications. Recent data also suggest a possible interest of WCD in monitoring patients, a finding that may prove useful in the context of new-onset heart failure. Data regarding WCD benefit is scarce, and definitive conclusions on its utility are hard to draw. In the context of heart failure, and particularly new-onset heart failure, WCD might find a role in a global comprehensive management of the disease, both acting as an educational tool, a monitoring tool, and, most importantly, a safe and effective tool in preventing sudden cardiac death. The low level of evidence however invites caution, and the decision of prescribing a WCD needs to be individualized and thoroughly discussed with the patient whose compliance is key with this device.

Early-stage heart failure disease prediction with deep learning approach

Cardiovascular diseases rank the highest among diseases in terms of mortality rate and cause millions of deaths every year. Heart failure is a type of cardiovascular disease and its early diagnosis is extremely important for its prevention. It may be vitally important to understand to what extent which body values, characteristics and factors (age, gender, blood pressure, sugar, etc.) affect this disease and to predict whether the individual will have a possible heart attack in the future. In this study, firstly, the correlation level of the relevant body values with the disease is extracted and in the second stage, a method that predicts heart attack with DNN (Deep Neural Network) and CNN (Convolutional Neural Network) deep learning models is proposed. In the study, 918 observations obtained from the kaggle site were used. Firstly, missing data, categorical data, non-numerical features were checked. Then, outliers were cleaned and the relationship of the features in the dataset with the disease state was revealed by feature engineering operations on the data. Finally, deep neural network models were built and the model was trained and hyperparameter adjustment was performed with GridSearhCV to achieve the highest success rate. As a result of the study, Accuracy, Precision, Recall and F1-Score values were found as 0.9375, 0.9629, 0.9176, 0.9397 for DNN and 0.9312, 0.9512, 0.9176, 0.9340 for CNN respectively. The AUC value calculated from the ROC curve was found to be equal to 0.96 in both deep learning models.

Chymase-independent vascular Ang-(1–12)/Ang II pathway and TXA2 generation are involved in endothelial dysfunction in the murine model of heart failure

The angiotensin (Ang)-(1–12)/Ang II pathway contributes to cardiac pathology. However, its involvement in the development of peripheral endothelial dysfunction associated with heart failure (HF) remains unknown. Therefore, this study aimed to characterise the effect of exogenous Ang-(1–12) and its conversion to Ang II on endothelial function using the murine model of HF (Tgαq*44 mice), focusing on the role of chymase and vascular-derived thromboxane A2 (TXA2).Ex vivo myographic assessments of isolated aorta showed impaired endothelium-dependent vasodilation in late-stage HF in 12-month-old Tgαq*44 mice. However, endothelium-dependent vasodilation was fully preserved in the early stage of HF in 4-month-old Tgαq*44 mice and 4- and 12-month-old FVB control mice. Ang-(1–12) impaired endothelium-dependent vasodilation in 4- and 12-month-old Tgαq*44 mice, that was associated with increased Ang II production. The chymase inhibitor chymostatin did not inhibit this response. Interestingly, TXA2 production reflected by TXB2 measurement was upregulated in response to Ang-(1–12) and Ang II in aortic rings isolated from 12-month-old Tgαq*44 mice but not from 4-month-old Tgαq*44 mice or age-matched FVB mice. Furthermore, in vivo magnetic resonance imaging showed that Ang-(1–12) impaired endothelium-dependent vasodilation in the aorta of Tgαq*44 mice and FVB mice. However, this response was inhibited by angiotensin I converting enzyme (ACE) inhibitor; perindopril, angiotensin II receptor type 1 (AT1) antagonist; losartan and TXA2 receptor (TP) antagonist-picotamide in 12-month-old-Tgαq*44 mice only.In conclusion, the chymase-independent vascular Ang-(1–12)/Ang II pathway and subsequent TXA2 overactivity contribute to systemic endothelial dysfunction in the late stage of HF in Tgαq*44 mice. Therefore, the vascular TXA2 receptor represents a pharmacotherapeutic target to improve peripheral endothelial dysfunction in chronic HF.

Exercise-induced pulmonary congestion is a promising marker to diagnose early stage heart failure in patients referred to rule out myocardial ischemia

Exercise-induced pulmonary congestion is a promising marker to diagnose early stage heart failure in patients referred to rule out myocardial ischemia

DEL-1 deficiency aggravates pressure overload-induced heart failure by promoting neutrophil infiltration and neutrophil extracellular traps formation

Recent studies have shown that neutrophils play an important role in the development and progression of heart failure. Developmental endothelial locus-1 (DEL-1) is an anti-inflammatory glycoprotein that has been found to have protective effects in various cardiovascular diseases. However, the role of DEL-1 in chronic heart failure is not well understood. In a mouse model of pressure overload-induced non-ischemic cardiac failure, we found that neutrophil infiltration in the heart increased and DEL-1 levels decreased in the early stages of heart failure. DEL-1 deficiency worsened pressure overload-induced cardiac dysfunction and remodeling in mice. Mechanistically, DEL-1 deficiency promotes neutrophil infiltration and the formation of neutrophil extracellular traps (NETs) through the regulation of P38 signaling. In vitro experiments showed that DEL-1 can inhibit P38 signaling and NETs formation in mouse neutrophils in a MAC-1-dependent manner. Depleting neutrophils, inhibiting NETs formation, and inhibiting P38 signaling all reduced the exacerbation of heart failure caused by DEL-1 deletion. Overall, our findings suggest that DEL-1 deficiency worsens pressure overload-induced heart failure by promoting neutrophil infiltration and NETs formation.

Exercise-induced pulmonary congestion is a promising marker to diagnose early stage heart failure in patients referred to rule out myocardial ischemia

Abstract Backgrounds Pulmonary congestion assessed by B-lines using lung ultrasound (LUS) is a hallmark of heart failure (HF). Latent HF at rest can be unmasked during exercise but the diagnosis remains challenging. Exercise-induced B-lines could help diagnose HF with preserved left ventricular ejection fraction (LVEF) at an early stage. The patients in whom coronary artery disease is suspected are also at risk of HF. Objectives To assess exercise-induced pulmonary congestion in patients referred to rule out myocardial ischemia. Methods Data of stress echocardiography combined with LUS at rest and immediately after exercise in patients with LVEF≥50% referred for investigation of inducible myocardial ischemia in a tertiary center of cardiology, during a 3-years period of time, were retrospectively analyzed. Patients with induced myocardial ischemia, hypertrophic cardiomyopathy or moderate to severe valvular disease were excluded. B-lines were assessed by scanning 2 chest sites. Exercise-induced pulmonary congestion was defined as an increase of B-lines ≥ 2 between baseline and exercise. Results A total of 1114 patients were included. Mean age was 63±11 years, 54% of patients had hypertension and 27% diabetes. Exercise-induced pulmonary congestion was identified in 131 (12%) patients. Age, left atrial volume index (LAVi), resting and 20W septal E/e’&amp;gt;15 and peak tricuspid regurgitation velocity (TRV) were associated with exercise-induced B-lines. In a multivariate logistic regression analysis, LAVi (Odds ratio (OR) = 1.03; 95%confidence interval (CI): 1.01–1.06; p = 0.003) and peak TRV (OR = 3.8; 95%CI: 1.4–10.1; p = 0.009) were independent predictors of exercise-induced pulmonary congestion. Conclusion Exercise-induced pulmonary congestion could be diagnosed in patients with preserved LVEF referred to rule out inducible myocardial ischemia. Exercise B-lines are linked with left ventricular diastolic dysfunction indices.

Predictors of Left Ventricular Ejection Fraction Improvement in Patients with Early-Stage Heart Failure with Reduced Ejection Fraction.

To identify the predictors of left ventricular ejection fraction (LVEF) recovery in patients with heart failure with reduced ejection fraction (HFrEF) and compare the mortality rate between patients with HFrEF and heart failure with improved ejection fraction (HFimpEF). Patients in a post-acute care program from 2018 to 2021 were enrolled. A series of echocardiograms were arranged during follow-up. Mortality, cardiovascular death and sudden cardiac death events were recorded. A total of 259 patients were enrolled and followed for at least 1 year; 158 (61%) patients fulfilled the criteria of HFimpEF, 87 (33.6%) were defined as having persistent HFrEF, and 14 (5.4%) were defined as having heart failure with mildly reduced ejection fraction. The patients with HFimpEF and persistent HFrEF were included for analysis. The mean follow-up duration was 1090 ± 414 days, and the median time to LVEF recovery was 159 days (IQR 112-289 days). Multivariate logistic regression analysis showed that beta-blocker prescription was the only independent predictor of HFimpEF [odds ratio (OR) 2.11, 95% confidence interval (CI) 1.10-4.08, p = 0.03]. Diagnosis of ischemic cardiomyopathy (ICM) and QRS duration ≥ 110 ms were negative predictors of HFimpEF (OR 0.49, 95% CI 0.27-0.88, p = 0.02, and OR 0.4, 95% CI 0.21-0.77, p = 0.005, respectively). The patients with HfimpEF had a significantly better prognosis with lower mortality (hazard ratio 0.2, 95% CI 0.08-0.50, log-rank p < 0.001) than the patients with persistent HFrEF. Beta-blocker prescription was an independent predictor of HFimpEF, while the diagnosis of ICM and QRS duration ≥ 110 ms were negative predictors of HFimpEF. Patients with HfimpEF had a significantly lower mortality rate compared to those with persistent HFrEF.

Estrategias de prevención de la insuficiencia cardiaca: enfoque integral en diferentes momentos de la enfermedad

Heart failure (HF) is considered a public health problem that affects a significant proportion of the population, especially older adults, leading to substantial morbidity, mortality, and high healthcare costs. Therefore, it becomes necessary to adopt prevention strategies from initial medical care and follow-up as a primary healthcare measure. With the aging population, the increase in cardiovascular risk factors in the general population, a higher survival rate after cardiovascular ischemic events, and an increase in life expectancy, the prevalence and incidence of HF is expected to rise in the upcoming years. The development of symptomatic heart failure is associated with a worsening prognosis despite treatment in accordance with current guidelines, making it a significant source of healthcare resource consumption. Hence, it is relevant to discuss the levels of HF prevention through interventions on risk factors, the disease's progression in those in the early stages of HF, as well as in those in the established and advanced stages of the disease to understand the impact of preventive measures on prognosis when implemented at different stages of the disease.

Nonsteroidal Mineralocorticoid Receptor Antagonist (Finerenone) in Cardiorenal Disease.

Nonsteroidal mineralocorticoid receptor antagonists (MRAs) present a promising therapeutic option in cardiorenal diseases, mitigating the limitations of steroidal MRAs. Finerenone, a third-generation nonsteroidal MRA, has demonstrated beneficial effects in heart failure (HF) and chronic kidney disease (CKD). Clinical trials, including FIDELIO-DKD and FIGARO-DKD, revealed finerenone's efficacy in improving kidney and cardiovascular (CV) outcomes. Patients with CKD and type 2 diabetes (T2DM) on finerenone experienced reduced rates of cardiovascular events, including hospitalization for HF. However, these trials excluded symptomatic HF patients, focusing on asymptomatic or early-stage HF. The ongoing FINEARTS-HF trial evaluates finerenone in HF with preserved ejection fraction (HFpEF). Additionally, studies exploring finerenone and sodium-glucose cotransporter 2 (SGLT2) inhibitors' (Empagliflozin) combination effects in CKD and T2DM (CONFIDENCE) and the selective MR modulator AZD9977 with another SGLT2 inhibitor (dapagliflozin) in HF and CKD (MIRACLE) aim to expand treatment options. While SGLT-2 inhibitors were shown to reduce hyperkalemia risk in FIDELIO-DKD and potentially lower new-onset HF incidence in FIGARO-DKD, further research is essential. So far, the evidence for the beneficial effect of finerenone in the spectrum of cardiorenal diseases is based only on the results of studies conducted in patients with T2DM, and clinical trials of finerenone in patients with nondiabetic kidney disease are ongoing. Nonsteroidal MRAs hold significant potential as pivotal treatment targets across the cardiorenal disease spectrum. This review will focus on the effects of finerenone on cardiorenal disease.

P-254 Cardiac and hidden toxicity of carfilzomib in presence of cardiometabolic syndrome and early-stage heart failure with reduced ejection fraction

P-254 Cardiac and hidden toxicity of carfilzomib in presence of cardiometabolic syndrome and early-stage heart failure with reduced ejection fraction

A profile on the CardioMEMS HF system in the management of patients with early stages of heart failure: an update

ABSTRACT Introduction Over the past decade, there have been noteworthy advances in the evaluation and treatment of heart failure (HF). Despite an improved understanding of this chronic disease, HF is still one of the leading causes of morbidity and mortality in the United States and worldwide. Decompensation and rehospitalization of HF patients remain an integral problem in disease management, with significant economic implications. Remote monitoring systems have been developed to detect HF decompensation early and address it before hospitalization. The CardioMEMS HF system is a wireless pulmonary artery (PA) monitoring system that detects changes in PA pressure and transmits data to the healthcare provider. As changes in PA pressures occur early during HF decompensation, the CardioMEMS HF system allows providers to institute timely changes in HF medical therapies to alter the course of the decompensation. The use of the CardioMEMS HF system has been shown to reduce HF hospitalization and improve quality of life. Areas Covered This review will focus on the available data supporting the expanded utilization of the CardioMEMS system in patients with HF. Expert Opinion The CardioMEMS HF system is a relatively safe and cost-effective device that reduces the incidence of HF hospitalization and qualifies as intermediate-to-high value medical care.

Effects of Mineralocorticoid Receptor Antagonists in Early-Stage Heart Failure With Preserved Ejection Fraction

BackgroundHospitalization with a first episode of heart failure (HF) is a serious event associated with poor clinical outcomes in HF with preserved ejection fraction (HFpEF). Identification of HFpEF via detection of elevated left ventricular filling pressure at rest or during exercise may allow early intervention. Benefits of treatment with mineralocorticoid receptor antagonists (MRAs) in established HFpEF have been reported, but use of MRAs is not well studied in early HFpEF without prior HF hospitalization. MethodsWe retrospectively studied 197 patients with HFpEF who did not have prior hospitalization but had been diagnosed by exercise stress echocardiography or catheterization. We examined changes in natriuretic peptide levels and echocardiographic parameters reflecting diastolic function following MRA initiation. ResultsOf the 197 patients with HFpEF, MRA treatment was initiated for 47 patients. After a median 3-month follow-up, reduction in N-terminal pro-B-type natriuretic peptide levels from baseline to follow-up was greater in patients treated with MRA than in those who were not (median, -200 pg/mL [interquartile range, -544 to -31] vs 67 pg/mL [interquartile range, -95 to 456], P < 0.0001 in 50 patients with paired data). Similar results were observed for the changes in B-type natriuretic peptide levels. Reduction in the left atrial volume index was also greater in the MRA-treated group than in the non-MRA-treated group after a median 7-month follow-up (77 patients with paired echocardiographic data). Patients with lower left ventricular global longitudinal strain experienced a greater reduction in N-terminal pro-B-type natriuretic peptide levels following MRA treatment. In the safety assessment, MRA modestly decreased renal function but did not change potassium levels. ConclusionsOur results suggest that MRA treatment has potential benefits for early-stage HFpEF.