Metabolic-Electrophysiological Coupling in Heart Failure: from Bidirectional Decoupling to Therapeutic Recoupling.

BackgroundAlthough contemporary guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) and heart failure with mildly-reduced ejection fraction (HFmrEF) has been shown to significantly improve prognosis, patients with these conditions still face considerable residual risk, and their quality of life (QoL) remains severely compromised. ShengXian-QuYu (SXQY) Decoction is a widely prescribed complementary and alternative medicine (CAM) therapy for HF in clinical practice. However, there is currently no robust evidence supporting its efficacy in HFrEF and HFmrEF, and its potential adverse effects have yet to be fully elucidated.MethodsPatients with chronic HF, New York Heart Association (NYHA) class II–IV symptoms, elevated plasma natriuretic peptide levels, and a left ventricular ejection fraction (LVEF) of ≤50 % were enrolled in the ShengXian-QuYu Decoction in the Treatment of Heart Failure with Reduced and mildly reduced Ejection Fraction (SHINE-HF) trial. Patients eligibility entered a run-in period, followed by randomization in a 1:1 ratio to double-blind treatment with either 30 ml of SXQY or 30 ml of placebo, administered twice daily. The primary endpoint was the change from baseline in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at week 12. Key secondary endpoints included the change from baseline in the Traditional Chinese Medicine Syndrome Score Scale (TCMSSS) and the 6-min walk test (6MWT) distance at week 12. Additionally, a safety analysis will be conducted.ConclusionSHINE-HF will determine the effects of SXQY on patient-reported outcomes (PROs) and symptom burden in patients with HFrEF and HFmrEF. This will shed light on the potential of SXQY as a novel treatment option in improving QoL of patients with HFrEF and HFmrEF.

Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk of morbidity and mortality. Sacubitril valsartan (previously known as LCZ696) is a new oral agent approved for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction. It is described as the first in class angiotensin receptor neprilysin inhibitor (ARNI) since it incorporates the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan. Neprilysin is an endopeptidase that breaks down several vasoactive peptides including natriuretic peptides (NPs), bradykinin, endothelin and angiotensin II (Ang-II). Therefore, a natural consequence of its inhibition is an increase of plasmatic levels of both, NPs and Ang-II (with opposite biological actions). So, a combined inhibition of these both systems (Sacubitril / valsartan) may enhance the benefits of NPs effects in HF (natriuresis, diuresis, etc) while Ang-II receptor is inhibited (reducing vasoconstriction and aldosterone release). In a large clinical trial (PARADIGM-HF with 8442 patients), this new agent was found to significantly reduce cardiovascular and all cause mortality as well as hospitalizations due to HF (compared to enalapril). This manuscript reviews clinical evidence for sacubitril valsartan, dosing and cautions, future directions and its considered place in the therapy of HF with reduced ejection fraction.

G Protein-Coupled Receptors-Receptors With New Tricks Up Their Sleeves.

The mechanism of decrease in dynamic mitral regurgitation during heart failure treatment: importance of reduction in the regurgitant orifice size.

The European Society of Cardiology Heart Failure Association Annual Congress.

Background Despite improvements in cancer management, cancer treatment related cardiac dysfunction (CTRCD) is a growing medical problem that impact cancer patients' prognosis, especially when it leads to early interruptions of effective anticancer therapies. Heart failure (HF) therapies are recommended in patients who develop symptomatic CTRCD or asymptomatic decrease in left ventricular ejection fraction (LVEF). However, the beneficial effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors was not prospectively tested in patients with cancer and CTRCD Purpose EMPACARD-treatment is a prospective registry aiming at evaluating the usefulness of empagliflozin on left ventricular remodelling in patients with metastatic breast cancer and refractory CTRCD. Methods Metastatic breast cancer patients, who develop refractory CTRCD during or after anthracycline chemotherapy and/or HER2 targeted therapies were prospectively included in our study and treated with empagliflozin 10mg/day on top of their current HF therapies. Refractory CTRCD was defined as symptomatic HF in patients treated with optimal doses of neurohormonal HF therapies, including sacubitril/valsartan. Clinical and echocardiographic variables were analysed to determine the potential benefits of empagliflozin on left ventricular remodelling (LVEF and left ventricular diastolic diameter (LVDD)), NT-proBNP levels, NHYA class and 6 minutes walking test (6MWT). The median follow-up was 6 months. Continuous variables were summarized as medians with interquartile ranges (IQR) and compared with Wilcoxon's test for paired samples. Categorical values were expressed as percentages and compared with the chi-squared test. Statistical significance was considered with a p-value of less than 0.05. All analyses were performed with R version 4.1.1. Results 19 metastatic breast cancer patients were included. Baseline characteristics and HF treatments are described in table 1. One patient received a heart transplant, and there were no deaths. At 6 months follow up LVEF significantly improved from 30% (IQR 27.5–32) to 38% (IQR (33.5–39), (p<0.001), NT-proBNP decreased from 1342 pg/ml (IQR (977–1756) to 784 pg/ml (IQR 641–1099.5) (p<0.0001), and similar improvements were observed in LVDD and 6MWT (Table 2). NYHA functional class improved in 95% of patients from class III to I or II at 6 months follow-up (p<0.003). Conclusions Guideline-based HF therapy, including empagliflozin improves LV remodelling in patients with cancer and refractory CTRCD. Empagliflozin might be a promising treatment option in patients with refractory CTRCD Funding Acknowledgement Type of funding sources: None.

Treatment of Diabetes in People with Heart Failure

Pulmonary artery pressure-based telemedicine in heart failure: ready for Europe?

AimsGuidelines recommend immediate initiation of all four class I guideline‐directed medical therapies, renin–angiotensin system inhibitors (RASI) or angiotensin receptor–neprilysin inhibitors (ARNI), beta‐blockers, mineralocorticoid receptor antagonists (MRA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) following the diagnosis of heart failure (HF) with reduced ejection fraction (HFrEF). The extent to which this occurs in new‐onset HFrEF is unclear. We assessed guideline‐recommended therapies during the first year following a HFrEF diagnosis.Methods and resultsThe Swedish HF Registry was linked to additional national registries. In patients with HFrEF (ejection fraction <40%), clinical characteristics and HF treatment from when they were available and recommended in guidelines were assessed according to time from HF diagnosis (<3, 3 to <6, 6–12 and >12 months). Of 55 581 patients with HFrEF enrolled between 2000 and 2021, 54%, 5.8%, 4.8% and 36% had an HF duration of <3, 3 to <6, 6–12 and >12 months, respectively. Patients with shorter HF duration were younger, had lower New York Heart Association class and had fewer cardiovascular comorbidities. Within 3 months, 3 to <6 months, 6–12 months and >12 months from HF diagnosis, 93%, 92%, 90% and 89% were on RASI or ARNI, 9.8%, 17%, 19% and 22% on ARNI alone, 35%, 43%, 44% and 46% on MRA, 92%, 92%, 92% and 91% on beta‐blockers, and 26%, 30%, 19% and 28% on SGLT2i, respectively. Additionally, 18% received cardiac resynchronization therapy/implantable cardioverter‐defibrillator >12 months after diagnosis.ConclusionsMost patients received RASI and beta‐blockers in the first months following HFrEF diagnosis. Use of ARNI, MRA and SGLT2i was limited, both in the early and later time periods. Our findings suggest that strategies to improve guideline‐directed use of HFrEF therapies remain urgently needed.

Mechanistic Efficacy of Sacubitril/Valsartan in Ischemic Versus Nonischemic HeartFailure.

Background: Recent advancements in heart failure (HF) therapy have significantly enhanced the management of patients across all phenotypes of left ventricular ejection fraction. However, these multidrug regimens frequently induce alterations in renal function by influencing intrarenal hemodynamics, thereby modifying glomerular capillary pressure. This phenomenon could result in a mild to moderate decline in estimated glomerular filtration rate (eGFR), often classified as “worsening kidney function.” This nomenclature stems from consistent observations of eGFR reductions recorded during HF treatment in clinical trials. This narrative review aims to elucidate why the observed eGFR declines in clinical practice may represent either loss of functioning glomeruli or pharmacologically mediated reductions in intraglomerular pressure that ultimately safeguards long-term renal and cardiovascular outcomes. Methods: By a comprehensive re-examination of data from HF clinical trials conducted with various classes of medications, all affecting eGFR, we sought to provide evidence that the decline in eGFR is associated with the activation of specific mechanisms that collectively contribute to a reduction in glomerular filtration pressure, a prominent factor in maladaptive neurohormonal responses. Results: From the investigation of angiotensin-converting enzyme inhibitors to the more recent non-steroidal mineralocorticoid receptor antagonist, the renal effects of these therapeutic regimens correlate with improvements in patient outcomes. The data consistently indicate that an early decline in eGFR, when coupled with an enhancement in HF outcomes, is associated with a more gradual decline in eGFR during long-term follow-up. Conclusions: Clinicians should recognize early declines in eGFR as indicators of favorable intraglomerular hemodynamic adjustments that mitigate maladaptive neurohormonal responses and contribute to improved long-term outcomes in patients with HF.

Heart Failure: A Palliative Medicine Review of Disease, Therapies, and Medications With a Focus on Symptoms, Function, and Quality of Life

Treatment of chronic heart failure (CHF) guided by natriuretic peptides has been studied in clinical trials with conflicting results. The aim of this study was to investigate if N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy in symptomatic heart failure patients in primary care would improve clinical outcomes over and above treatment according to guidelines. SIGNAL-HF was a 9 month, randomized, single-blind, parallel group study in patients with CHF in NYHA class II-IV, ejection fraction (EF)<50% and elevated NT-proBNP levels (males>800, females>1000 ng/L). All investigators underwent a pre-study educational programme about current CHF guidelines. A control group managed by non-trained investigators was considered not possible for ethical and practical reasons. Patients were randomized to structured treatment of CHF according to guidelines with or without NT-proBNP monitoring. The choice and dose of therapy for CHF was at the investigator's discretion. The primary outcome variable was the composite endpoint of days alive, days out of hospital, and symptom score from the Kansas City Cardiomyopathy Questionnaire. In all, 252 patients were randomized. The allocation groups were well balanced with regards to age, NT-proBNP, and EF. Treatment doses of beta-blockers and blockers of the renin-angiotensin-aldosterone system were markedly increased towards target doses and to a similar degree in both groups. There were no differences between the groups concerning either the primary endpoint (P=0.28) or its components [cardiovascular (CV) death, P=0.93; CV hospitalization, P=0.88; or symptom score, P=0.28]. NT-proBNP-guided CHF treatment did not result in important improvements in clinical outcomes in patients with CHF in primary care above and beyond what could be achieved by education and structured CHF treatment according to guidelines.

Beta blocker treatment in heart failure

Cardiac Resynchronization Therapy