Clinical Interventions and Hemodynamic Monitoring in the Setting of Left Ventricular Systolic Heart Failure in Children: Insights From a Physiologic Simulator.

BACKGROUND: In pediatric critical care, vasoactive/inotropic support is widely used in patients with heart failure, but it remains controversial because the influence of multiple medications and the interplay between their inotropic and vasoactive effects on a given patient are hard to predict. Robust evidence supporting their use and quantifying their effects in this group of patients is scarce. STUDY QUESTION: The aim of this study was to characterize the effect of vasoactive medications on various cardiovascular parameters in pediatric patient with decreased ejection fraction. STUDY DESIGN: Clinical-data based physiologic simulator study. MEASURE AND OUTCOMES: We used a physics-based computer simulator for quantifying the response of cardiovascular parameters to the administration of various types of vasoactive/inotropic medications in pediatric patients with decreased ejection fraction. The simulator allowed us to study the impact of increasing medication dosage and the simultaneous administration of some vasoactive agents. Correlation and linear regression analyses yielded the quantified effects on the vasoactive/inotropic support. RESULTS: Cardiac output and systemic venous saturation significantly increased with the administration of dobutamine and milrinone in isolation, and combination of milrinone with dobutamine, dopamine, or epinephrine. Both parameters decreased with the administration of epinephrine and norepinephrine in isolation. No significant change in these hemodynamic parameters was observed with the administration of dopamine in isolation. CONCLUSIONS: Milrinone and dobutamine were the only vasoactive medications that, when used in isolation, improved systemic oxygen delivery. Milrinone in combination with dobutamine, dopamine, or epinephrine also increased systemic oxygen delivery. The induced increment on afterload can negatively affect systemic oxygen delivery.

Obesity in Heart Failure with Reduced Ejection Fraction: Time to Address the Elephant in the Room.

Obesity has been long recognized as a risk factor for the development of heart failure, but recent evidence suggests obesity is more typically associated with heart failure with preserved ejection fraction as opposed to heart failure with reduced ejection fraction (HFrEF). Nevertheless, numerous studies have found that obesity modulates the presentation and progression of HFrEF and may contribute to the development of HFrEF in some patients. Although obesity has definite negative effects in HFrEF patients, the effects of intentional weight loss in HFrEF patients with obesity have been poorly studied.

Who Can Receive Clinical Benefit from Mid-Term Vericiguat Add-on Therapy Among Patients with Systolic Heart Failure Receiving Quadruple Medical Therapy?

Vericiguat, a soluble guanylate cyclase stimulator known for augmenting cyclic guanosine monophosphate production, has garnered substantial clinical attention in patients with systolic heart failure. Despite its proven efficacy, discerning the specific subset of individuals who can enjoy clinical advantages from vericiguat therapy in contemporary real-world clinical practice, particularly among the individuals undergoing "quadruple medical therapy" comprising administration of a beta-blocker, angiotensin receptor neprilysin inhibitor, mineralocorticoid receptor antagonist, and sodium-glucose co-transporter 2 inhibitor, remains an unresolved query. This study involved patients undergoing 3-month vericiguat therapy alongside complete quadruple medical therapy in a contemporary real-world clinical practice. Baseline characteristics associated with the primary outcome, defined as a reduction in serum NT pro-B-type natriuretic peptide (BNP) levels over the 3-month therapeutic duration, were scrutinized. A cohort of 24 patients (median age: 66 years; 20 males) were included. All participants diligently adhered to the 3-month vericiguat therapy in conjunction with the quadruple medical regimen. A higher baseline systolic blood pressure emerged as an independent factor linked to the primary outcome, yielding an adjusted odds ratio of 1.31 (95% confidence interval: 1.03-1.65, P = 0.026) at a threshold of 105 mmHg. This threshold notably stratified the trajectories of serum NT pro-BNP levels during the 3-month vericiguat therapy. In conclusion, preservation of baseline systolic blood pressure emerged as a pivotal determinant for reaping the clinical benefits from mid-term vericiguat therapy among patients with systolic heart failure receiving quadruple medical therapy.

The Impact of Midodrine on Guideline-Directed Medical Therapy in Patients Admitted With Systolic Heart Failure.

ABSTRACT: Midodrine is occasionally used off-label to treat hypotension associated with advanced heart failure (HF); however, its association with changes in prescription of guideline-directed medical therapy (GDMT) is unknown. We sought to evaluate the effect of midodrine on the GDMT prescription pattern and clinical outcomes of patients with decompensated systolic HF. We retrospectively identified 114 patients admitted to our hospital in 2020 with decompensated systolic HF who were prescribed midodrine on discharge and compared them with 358 patients with decompensated systolic HF who were not prescribed midodrine. At 6 months, the midodrine group had more initiation or up-titration of beta blockers, renin-angiotensin-aldosterone system inhibitors, and sodium-glucose cotransporter-2 inhibitors compared with the nonmidodrine group. Survival at 6 months was similar between the 2 groups, but the midodrine group had more frequent rehospitalization for HF. Our findings suggest that midodrine is associated with improved GDMT in patients with decompensated HF but may be associated with worse prognosis.

High Risk of Stroke in Patients With Worsening Heart Failure, Reduced Ejection Fraction, Coronary Heart Disease and Sinus Rhythm: Risk Prediction Score Analysis From the COMMANDER-HF Trial.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and sinus rhythm have a heightened risk of stroke. Whether anticoagulation benefits these patients is uncertain. In this post hoc analysis of the A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure (COMMANDER-HF) trial we evaluated how a previously validated risk model consisting of 3 variables (history of prior stroke, insulin-treated diabetes, and N-terminal pro-B-type natriuretic peptide level) would perform, compared with plasma d-dimer, for stroke prediction and estimation of the benefit of low-dose rivaroxaban. METHODS AND RESULTS: Stroke risk and treatment effect were computed across risk score and plasma d-dimer tertiles. Risk score was available in 58% of the COMMANDER-HF population (n = 2928). Over a median follow-up of 512 days (range 342-747 days), 60 patients experienced a stroke (14.6 per 1000 patient-years). The risk model did not identify patients at higher risk of stroke and showed a low overall prognostic performance (C-index = 0.53). The effect of rivaroxaban on stroke was homogeneous across risk score tertiles (P-interaction = .67). Among patients in whom the risk score was estimated, d-dimer was available in 2343 (80%). d-dimer had an acceptable discrimination performance for stroke prediction (C-index = 0.66) and higher plasma d-dimer concentrations were associated with higher rates of stroke (ie, tertile 3 vs tertile 1, hazard ratio 3.65, 95% confidence interval 1.59-8.39, P = .002). Treatment with low-dose rivaroxaban reduced the incidence of stroke in patients at highest risk by d-dimer levels (ie, >515 ng/mL, hazard ratio 0.42, 95% confidence interval 0.18-0.95, P-interaction = .074), without any safety concerns. CONCLUSIONS: In our analysis, plasma d-dimer concentrations performed better than a previously described 3-variable risk score for stroke prediction in patients with heart failure with reduced ejection fraction, a recent clinical worsening and sinus rhythm as enrolled in the COMMANDER-HF trial. In these patients, a raised plasma d-dimer concentration identified patients who might benefit most from rivaroxaban.

Financial Implication of Sodium Zirconium Cyclosilicate Therapy in Patients with Systolic Heart Failure and Hyperkalemia.

Sodium zirconium cyclosilicate (SZC), a newly-introduced potassium binder, can be used to manage hyperkalemia especially in patients with chronic kidney disease and in those on medical therapy which may raise serum potassium levels. The medication may incur additional costs but may in turn have a significant benefit in the effect of maintaining guideline-directed medical therapy for heart failure. We aimed to investigate the financial impact of SZC therapy in patients with systolic heart failure.Patients with systolic heart failure who received SZC for hyperkalemia between July 2020 and March 2023 were included. In-hospital medical costs were compared between the patients who discontinued SZC and those who continued SZC. For the continue group, the cost of SZC was added. All patients were followed for 2 years or until May 2023.A total of 36 patients (median age 81 years, 56% male, median left ventricular ejection fraction 43%) were included. Total medical costs were significantly lower in the continue group (n = 12) compared to the discontinue group (n = 24) (3.1 [3.1, 6.2] versus 12.1 [3.8, 48.6] × 104 JPY per month, P = 0.039). In the continue group, serum potassium levels were decreased, renin-angiotensin-aldosterone system inhibitor doses were up-titrated, and the left ventricular ejection fraction was increased, whereas these parameters remained unchanged or worsened in the discontinue group.SZC may have the potential to assist in the up-titration of potassium-sparing heart failure-specific medications, prevent readmissions, and minimize medical costs, by preventing recurrent hyperkalemia in patients with systolic heart failure.

Sacubitril/Valsartan Cannot Improve Cardiac Function Compared with Valsartan in Patients Suffering Nonvalvular Atrial Fibrillation without Systolic Heart Failure.

This study investigates the effect of sacubitril/valsartan (Sac/Val) in patients diagnosed with nonvalvular atrial fibrillation (AF) without systolic heart failure (SHF).Nonvalvular AF patients without SHF admitted to the People's Hospital of Bortala Mongol Autonomous Prefecture from December 2020 to December 2021 were enrolled and randomly divided into Sac/Val treatment group (group T) and valsartan treatment group (group C, control). For subgroup analysis, patients were divided into subgroups with and without diastolic heart failure (DHF). After 1-month adaptive phase and subsequent 3-month treatment period, patients were followed up in the cardiology clinic. Plasma levels of biochemical markers and echocardiographic parameters before and after treatment were evaluated, and DHF scores were computed to assess diastolic function.Of 61 enrolled patients, 46 patients completed follow-up. Sac/Val treatment did not increase the percentage of sinus rhythm. Although N-terminal pro-B-type natriuretic peptide (NT-proBNP) expression tended to be reduced in both groups after 3 months of treatment, the differences compared with respective baseline levels and between groups were not significant. According to subgroup analysis, although NT-proBNP expression in the subgroup with DHF was lower at follow-up compared to baseline, the difference was not statistically significant. Similarly, no marked differences in echocardiographic parameters or tissue Doppler parameters related to DHF were detected between the groups (P > 0.05). Additionally, a subgroup analysis found no significant variations in the echocardiographic measures (P > 0.05).Sac/Val is not superior to valsartan for the short-term treatment of patients suffering with AF without SHF in improving NT-proBNP level and cardiac function.

Beta-blocker use and mortality among patients with systolic heart failure and pacemaker rhythm.

AIMS: Beta-blockers are proven to improve survival among patients with heart failure with reduced ejection fraction. Their efficacy in patients with heart failure with reduced ejection fraction and pacemaker devices has not been demonstrated. Our aim was to test the hypothesis that beta-blocker therapy is associated with improved survival in patients with chronic heart failure and a pacemaker rhythm on electrocardiogram (ECG). METHODS AND RESULTS: This is a post hoc analysis from the GISSI-HF randomized clinical trial. We evaluated efficacy of beta-blockers by creating Cox proportional hazards models adjusting for pacemaker rhythm and heart rate, among other variables. Interactions between pacemaker rhythm, heart rate, and beta-blocker were also examined. Of the 6975 patients enrolled in the GISSI-HF trial, 813 (11.7%) had a pacemaker rhythm on baseline ECG. Of these 813 patients, 511 (62.9%) were receiving beta-blocker therapy. The effect of beta-blocker therapy on mortality was assessed using multivariable Cox proportional hazards adjusted for 27 co-variates. In the whole cohort, beta-blocker therapy was significantly associated with reduced mortality (hazard ratio 0.79 [0.72-0.87], P < 0.001), without interaction between beta-blockers, pacemaker rhythm and heart rate. Beta-blocker therapy was beneficial in the sub-group restricted to baseline pacemaker rhythm (hazard ratio 0.62 [0.49-0.79], P < 0.001). CONCLUSIONS: Beta-blocker therapy is associated with improved survival among patients with heart failure and a pacemaker rhythm on ECG. Further studies are necessary to analyse differences between atrial and ventricular pacemakers.

The effect of a standardized capsule of Aloe vera gel on the quality of life in patients with systolic heart failure: A randomized double-blind placebo-controlled clinical trial.

This trial was designed to evaluate the effect of a standardized capsule of Aloe vera gel (AVG) on the quality of life (QOL) in patients with systolic heart failure (HF). Forty-two patients were randomly divided into two groups to receive either AVG 150 mg or harmonized placebo capsules twice a day for 8 weeks. The patients were evaluated before and after the intervention using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association (NYHA) functional class, six-minute walk test (6MWT), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI) and STOP-BANG questionnaires. Post-intervention, AVG group indicated a significant reduction in the total score of MLHFQ (p < 0.001). The changes in MLHFQ and NYHA class were statistically significant after taking medication (p < 0.001 and p = 0.004, respectively). The change of 6MWT in the AVG group was more advanced; however, it was not statistically significant (p = 0.353). Moreover, in the AVG group, the severity of insomnia and obstructive sleep apnea decreased (p < 0.001, p = 0.01 respectively) and the sleep quality improved as well (p < 0.001). There were significantly fewer adverse events reported in the AVG group (p = 0.047). Therefore, AVG combined with standard medical therapy could provide more clinical benefits for patients with systolic HF.