Latest pharmaceutical approaches across the spectrum of heart failure.

Despite major advances in prevention and medical therapy, heart failure (HF) remains associated with high morbidity and mortality, especially in older and frailer patients. Therefore, a complete, guideline-based treatment is essential, even in HF patients with conditions traditionally associated with a problematic initiation and escalation of the medical HF therapy, such as chronic kidney disease and arterial hypotension, as the potential adverse effects are overcome by the overall decrease of the absolute risk. Furthermore, since the latest data suggest that the benefit of a combined medical therapy (MRA, ARNI, SGLT2i, beta-blocker) may extend up to a LVEF of 65%, further trials on these subgroups of patients (HFmrEF, HFpEF) are needed to re-evaluate the guideline-directed medical therapy across the HF spectrum. In particular, the use of SGLT2i was recently extended to HFpEF patients, as evidenced by the DELIVER and EMPEROR-preserved trials. Moreover, the indication for other conservative treatments in HF patients, such as the intravenous iron supplementation, was accordingly strengthened in the latest guidelines. Finally, the possible implementation of newer substances, such as finerenone, in guideline-directed medical practice for HF is anticipated with great interest.

Successful transcatheter aortic valve replacement in a failing HAART 300 aortic valve annuloplasty ring: A case report.

Transcutaneous aortic valve replacement (TAVR) has evolved from a complex procedure meant only for patients at prohibitive risk for surgery to a commonly performed procedure across a wide variety of clinical scenarios including the treatment of failed aortic valve bioprosthesis. Annuloplasty rings in the aortic position such as HAART 300 (Biostable Science and Engineering) have been introduced in the management of native aortic regurgitation. Percutaneous management of failed bioprosthesis rings in the aortic position has not been widely described. We present a case of a 69-year-old man with recurrent aortic regurgitation successfully treated with TAVR using a SAPIEN 3 valve within a HAART 300 ring.

Differences in provider approach to initiating and titrating guideline directed medical therapy in heart failure with reduced ejection fraction.

BACKGROUND: Despite the strong evidence supporting guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction (HFrEF), prescription rates in clinical practice are still lacking. METHODS: A survey containing 20 clinical vignettes of patients with HFrEF was answered by a national sample of 127 cardiologists and 68 internal/family medicine physicians. Each vignette had 4-5 options for adjusting GDMT and the option to make no medication changes. Survey respondents could only select one option. For analysis, responses were dichotomized to the answer of interest. RESULTS: Cardiologists were more likely to make GDMT changes than general medicine physicians (91.8% vs. 82.0%; OR 1.84 [1.07-3.19]; p = 0.020). Cardiologists were more likely to initiate beta-blockers (46.3% vs. 32.0%; OR 2.38 [1.18-4.81], p = 0.016), angiotensin receptor blocker/neprilysin inhibitor (ARNI) (63.8% vs. 48.1%; OR 1.76 [1.01-3.09], p = 0.047), and hydralazine and isosorbide dinitrate (HYD/ISDN) (38.2% vs. 23.7%; OR 2.47 [1.48-4.12], p < 0.001) compared to general medicine physicians. No differences were found in initiating angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEi/ARBs), initiating mineralocorticoid receptor antagonist (MRA), sodium-glucose transporter protein 2 (SGLT2) inhibitors, digoxin, or ivabradine. CONCLUSIONS: Our results demonstrate cardiologists were more likely to adjust GDMT than general medicine physicians. Future focus on improving GDMT prescribing should target providers other than cardiologists to improve care in patients with HFrEF.

Beyond Quadruple Therapy and Current Therapeutic Strategies in Heart Failure with Reduced Ejection Fraction: Medical Therapies with Potential to Become Part of the Therapeutic Armamentarium.

Heart failure with reduced ejection fraction (HFrEF) is a complex clinical syndrome with significant morbidity and mortality and seems to be responsible for approximately 50% of heart failure cases and hospitalizations worldwide. First-line treatments of patients with HFrEF, according to the ESC and AHA guidelines, include ß-blockers, angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists. This quadruple therapy should be initiated during hospital stay and uptitrated to maximum doses within 6 weeks after discharge according to large multicenter controlled trials. Quadruple therapy improves survival by approximately 8 years for a 55-year-old heart failure patient. Additional therapeutic strategies targeting other signaling pathways such as ivabradine, digoxin, and isosorbide dinitrate and hydralazine combination for African Americans, as well as adjunctive symptomatic therapies, seem to be necessary in the management of HFrEF. Although second-line medications have not achieved improvements in mortality, they seem to decrease heart failure hospitalizations. There are novel medical therapies including vericiguat, omecamtiv mecarbil, genetic and cellular therapies, and mitochondria-targeted therapies. Moreover, mitraclip for significant mitral valve regurgitation, ablation in specific atrial fibrillation cases, omecamtiv mecarbil are options under evaluation in clinical trials. Finally, the HeartMate 3 magnetically levitated centrifugal left ventricular assist device (LVAD) has extended 5-year survival for stage D HF patients who are candidates for an LVAD.

Right Ventricular Ejection Fraction and Beta-Blocker Effect in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown. METHODS AND RESULTS: Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75-1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78-1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55-0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83-1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251). CONCLUSIONS: The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.

SGLT-2 Inhibitors for Patients with Heart Failure: What Have We Learned Recently?

PURPOSE OF REVIEW: In this review, we discuss the mechanisms of action of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the purported protective effects for mitigating heart failure (HF)-related outcomes. RECENT FINDINGS: Major randomized clinical trials have demonstrated the cardiovascular safety and efficacy of SGLT-2i among patients without known HF and those with established HF with reduced ejection fraction or preserved ejection fraction (HFrEF and HFpEF respectively). Recent HF guidelines have incorporated SGLT-2i in HF treatment algorithms. SGLT-2i have emerged as a novel treatment for both prevention of HF and reduction of cardiovascular morbidity and mortality among patients with existing HFrEF or HFpEF.

Incidence and Risk Factors of Future Need for Long-Term Care Insurance in Japanese Elderly Patients With Left Ventricular Systolic Dysfunction.

BACKGROUND: Heart failure in elderly people causes physical and cognitive dysfunction and often requires long-term care insurance (LTCI); however, among patients with left ventricular (LV) systolic dysfunction, the incidence and risk factors of future LTCI requirements need to be elucidated.Methods and Results:The study included 1,852 patients aged ≥65 years with an echocardiographic LV ejection fraction (LVEF) ≤50%; we referred to their LTCI data and those of 113,038 community-dwelling elderly people. During a mean 1.7-year period, 332 patients newly required LTCI (incidence 10.7 per 100 person-years); the incidence was significantly higher than that for the community-dwelling people (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.32-1.64). On multivariate analysis, the risk factors at the time of echocardiography leading to future LTCI requirement were atrial fibrillation (HR, 1.588; 95% CI, 1.279-1.971), history of stroke (HR, 2.02; 95% CI, 1.583-2.576), osteoporosis (HR, 1.738; 95% CI, 1.253-2.41), dementia (HR, 2.804; 95% CI, 2.075-3.789), hypnotics (HR, 1.461; 95% CI, 1.148-1.859), and diuretics (HR, 1.417; 95% CI, 1.132-1.773); however, the LVEF was not a risk factor (HR, 0.997; 95% CI, 0.983-1.011). CONCLUSIONS: In elderly patients with LV systolic dysfunction, the incidence of LTCI requirement was more common than that for community-dwelling people; its risk factors did not include LVEF, but included many other non-cardiac comorbidities and therapies, suggesting the need for interdisciplinary cooperation to prevent disabilities.

Trends in Kidney Function Outcomes Following RAAS Inhibition in Patients With Heart Failure With Reduced Ejection Fraction.

RATIONALE & OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors are beneficial in heart failure with reduced ejection fraction (HFrEF). We sought to describe longitudinal trends in estimated glomerular filtration rate (eGFR) in HFrEF and how ACE-inhibitor therapy influences these changes. STUDY DESIGN: Post hoc analysis of trial data. SETTINGS & PARTICIPANTS: Symptomatic (Treatment Trial, n=2,423) and asymptomatic (Prevention Trial, n=4,094) patients from the Studies of Left Ventricular Dysfunction (SOLVD). EXPOSURE: Enalapril versus placebo. OUTCOMES: Early and long-term eGFR slope (ie, within and after the first 6 weeks) and 4 kidney end points: (1) serum creatinine level increase by≥0.3mg/dL, (2)>30% eGFR decline, (3)>40% eGFR decline, and (4) incident eGFR<30mL/min/1.73m2. ANALYTICAL APPROACH: Shared parameter models, multivariable Cox regression models. RESULTS: Baseline mean eGFR was lower in the Treatment Trial than in the Prevention Trial, 69.5±19.8 (SD) versus 76.2±18.6mL/min/1.73m2. Following randomization, an early eGFR decline occurred in the enalapril group; however, slopes during the median 3-year follow-up were not statistically different by randomization arm in either the Treatment Trial (-0.84 in enalapril vs-1.36mL/min/1.73m2 per year in placebo; P=0.08) or Prevention Trial (-1.27 in enalapril vs-1.36mL/min/1.73m2 per year in placebo; P=0.7). Random assignment to enalapril treatment increased the risk for all 4 outcomes in the Treatment Trial in the first 6-week period (HRs were 1.48 [95% CI, 1.10-1.99] for creatinine increase by≥0.3mg/dL; 1.38 [95% CI, 0.98-1.94] for eGFR decline> 30%; 2.60 [95% CI, 1.30-5.21] for eGFR decline> 40%; and 4.71 [95% CI, 1.78-12.50] for eGFR<30mL/min/1.73m2), but after the first year was not significantly associated with increased risk. A similar albeit less pronounced pattern was observed in the Prevention Trial, with risks present only in the early period. LIMITATIONS: Creatinine results were not blinded, making it possible that ACE-inhibitor/placebo dosing was influenced by creatinine level. CONCLUSION: Kidney function decline is slow in HFrEF. Although random assignment to enalapril treatment results in a statistically increased risk for kidney surrogates, the risk is limited to the early phase and late eGFR slopes and risks are not different by randomly assigned group.

Ischemia and Viability Testing in New-Onset Heart Failure.

PURPOSE OF REVIEW: To examine the utility and methods of coronary artery disease (CAD) assessment in patients with new-onset heart failure with reduced ejection fraction (HFrEF) of unclear etiology. Moreover, we sought to review the role and techniques of assessing myocardial viability to guide coronary revascularization in patients with established ischemic cardiomyopathy. RECENT FINDINGS: Data indicates that surgical coronary revascularization in patients with HFrEF due to ischemic cardiomyopathy leads to lower long-term all-cause mortality and cardiovascular hospitalizations. Thus, identifying ischemic heart disease in patients with new-onset HFrEF is essential. In addition to invasive coronary angiography (ICA), radionuclide myocardial perfusion imaging, coronary CT angiography (CCTA), and cardiac magnetic resonance (CMR) imaging have emerged as effective non-invasive tools in the assessment of CAD in this population. Viability testing remains an area of particular interest and debate and its full potential has not been fully addressed. We propose stepwise algorithms for CAD and viability assessment in this patient population. Non-invasive testing with radionuclide myocardial perfusion imaging, CCTA, and CMR is an alternative to ICA for CAD assessment in patients with new-onset HFrEF of unclear etiology. Several non-invasive imaging modalities have proved to be effective in detecting viable myocardium in patients with ischemic cardiomyopathy. The use of viability imaging to guide coronary revascularization should be individualized.

Acute Decompensated Heart Failure in Patients with Heart Failure with Reduced Ejection Fraction.

Acute decompensated heart failure (ADHF) requires immediate treatments because it impairs perfusion to systemic organs and their function. Half of all patients with ADHF are diagnosed with heart failure with reduced left ventricular ejection fraction (HFrEF). The initial goal of management for ADHF is to stabilize hemodynamic status. Pulmonary edema is treated with vasodilators or diuretics. Inhibitors of the renin-angiotensin-aldosterone system and ß-blockers should be started and/or increased to meet the maximum dose, ideally the target dose, that the patient can tolerate as a treatment of HFrEF. Patients with severe circulatory failure need inotropic drugs or mechanical circulatory support.

Ankle-brachial index and incident heart failure with reduced versus preserved ejection fraction: The Multi-Ethnic Study of Atherosclerosis.

This study investigated the relationship between ankle-brachial index (ABI) and risk for heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). ABI has previously been associated with mortality, cardiovascular disease (CVD), and overall HF but the relationship between ABI and risk of HF stratified by EF has not been well characterized. We analyzed data from 6553 participants (53% female; mean age 62 ± 10 years) enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of known clinical CVD/HF at baseline (2000-2002) and had baseline ABI measured. Participants were classified as low (≤ 0.90), borderline-low (0.91-1.00), normal (1.01-1.40), and high (> 1.40) ABI. Incident hospitalized HF was determined over a median follow-up of 14 years; we classified HF events (n = 321) as HFrEF with EF < 50% (n = 155, 54%) or HFpEF with EF ⩾ 50% (n = 133, 46%). Low ABI was associated with incident HFrEF (hazard ratio (HR): 2.02, 95% CI 1.19-3.40, p = 0.01) and had no significant association with HFpEF (HR: 0.67, 95% CI 0.30-1.48, p = 0.32). Borderline-low and high ABI were not significantly associated with HFrEF or HFpEF. Cubic spline analyses showed association with both low and high ABI for HFrEF and high ABI for HFpEF. A 1 SD lower ABI (for ABI < 1.1) was associated with incident HFrEF in multivariable analysis (HR: 1.27, 95% CI 1.05-1.54) but was not significant after additionally adjusting for interim myocardial infarction (HR: 1.21, 95% CI 0.99-1.48). Low ABI was associated with higher risk for incident HFrEF but not HFpEF in persons free of known CVD. Future studies of a larger size are needed for high ABI analyses.

The Evolution from Hypertension to Heart Failure.

Hypertensive heart disease includes the development of diastolic dysfunction, left ventricular hypertrophy, and heart failure with preserved and reduced ejection fraction. The development of heart failure can occur because of complications of ischemic heart disease or from progression of diastolic dysfunction to heart failure with preserved ejection fraction degenerating to a dilated heart with systolic dysfunction or heart failure with reduced ejection fraction. Hypertension clinical trials have shown that the treatment of hypertension can prevent the development of heart failure. In addition, lifestyle modification with exercise and weight loss can improve diastolic function and reduce the risk for heart failure.

Pathophysiological and therapeutic implications in patients with atrial fibrillation and heart failure.

Heart failure and atrial fibrillation are common and responsible for significant mortality of patients. Both share the same risk factors like hypertension, ischemic heart disease, diabetes, obesity, arteriosclerosis, and age. A variety of microscopic and macroscopic changes favor the genesis of atrial fibrillation in patients with preexisting heart failure, altered subcellular Ca2+ homeostasis leading to increased cellular automaticity as well as concomitant fibrosis that are induced by pressure/volume overload and altered neurohumoral states. Atrial fibrillation itself promotes clinical deterioration of patients with preexisting heart failure as atrial contraction significantly contributes to ventricular filling. In addition, atrial fibrillation induced tachycardia can even further compromise ventricular function by inducing tachycardiomyopathy. Even though evidence has been provided that atrial functions significantly and independently of confounding ventricular pathologies, correlate with mortality of heart failure patients, rate and rhythm controls have been shown to be of equal effectiveness in improving mortality. Yet, it also has been shown that cohorts of patients with heart failure benefit from a rhythm control concept regarding symptom control and hospitalization. To date, amiodarone is the most feasible approach to restore sinus rhythm, yet its use is limited by its extensive side-effect profile. In addition, other therapies like catheter-based pulmonary vein isolation are of increasing importance. A wide range of heart failure-specific therapies are available with mixed impact on new onset or perpetuation of atrial fibrillation. This review highlights pathophysiological concepts and possible therapeutic approaches to treat patients with heart failure at risk for or with atrial fibrillation.

Safety of midodrine in patients with heart failure with reduced ejection fraction: a retrospective cohort study.

Background: Heart failure with reduced ejection fraction (HFrEF) poses significant health risks. Midodrine for maintaining blood pressure in HFrEF, requires further safety investigation. This study explores midodrine's safety in HFrEF through extensive matched analysis. Methods: Patients with HFrEF (LVEF <50%) without malignancy, non-dialysis dependence, or non-orthostatic hypotension, were enrolled between 28 August 2013, and 27 August 2023. Propensity score matching (PSM) created 1:1 matched groups. Outcomes included mortality, stage 4 and 5 chronic kidney disease (CKD), emergency room (ER) visits, intensive care unit (ICU) admissions, hospitalizations, and respiratory failure. Hazard ratios (HR) with 95% confidence intervals (95% CI) were calculated for each outcome, and Kaplan-Meier survival analysis was performed. Subgroup analyses were conducted based on gender, age (20-<65 vs. ≥65), medication refill frequency, and baseline LVEF. Results: After 1:1 PSM, 5813 cases were included in each group. The midodrine group had higher risks of respiratory failure (HR: 1.16, 95% CI: 1.08-1.25), ICU admissions (HR: 1.14, 95% CI: 1.06-1.23), hospitalizations (HR: 1.21, 95% CI: 1.12-1.31), and mortality (HR: 1.090, 95% CI: 1.01-1.17). Interestingly, midodrine use reduced ER visits (HR: 0.77, 95% CI: 0.71-0.83). Similar patterns of lower ER visit risk and higher risks for ICU admissions, respiratory failure, and overall hospitalizations were observed in most subgroups. Conclusion: In this large-scale study, midodrine use was associated with reduced ER visits but increased risks of respiratory failure, prolonged ICU stays, higher hospitalizations, and elevated mortality in HFrEF patients. Further research is needed to clarify midodrine's role in hemodynamic support and strengthen existing evidence.

The Clinical Effects of Pharmacotherapy Combined with Blood Flow Restriction and Isometric Exercise Training in Rehabilitating Patients with Heart Failure with Reduced Ejection Fraction.

Heart failure with reduced ejection fraction (HFrEF) is associated with reduced cardiac function and impaired quality of life. Blood flow restriction (BFR) training is emerging as a potential adjunctive therapy. This study aimed at evaluating the efficacy of combination of BFR and isometric exercises on cardiac function, functional status, and quality of life in HFrEF patients. Totally 44 patients with HFrEF were equally divided into a control group and a combined treatment group. Both groups received standard pharmacotherapy and upper limb exercise, with the combined group also undergoing BFR and isometric exercise training. We assessed demographic and clinical characteristics, New York Heart Association (NYHA) functional classification, cardiac function parameters, serum Brain Natriuretic Peptide levels, physical capacity via the 6-minute walking test, and quality of life using the Heart Failure Questionnaire (Minnesota Living with Heart Failure Questionnaire). Post-treatment, the combined group significantly improved in NYHA classification (p = 0.012), with more patients shifting to a better class. Cardiac function improved in both groups, with the combined group showing a greater increase in mean left ventricular ejection fractions (p < 0.001), and reductions in left ventricular end-diastolic and end-systolic diameters (p < 0.05). The addition of BFR training to standard pharmacotherapy with upper limb exercise in HFrEF patients led to significant enhancements in cardiac function, functional status, and quality of life. These findings support the integration of BFR training into conventional HFrEF treatment regimens to maximize patient recovery outcomes.

Asymptomatic vs Symptomatic Hypotension With Sacubitril/Valsartan in Heart Failure and Reduced Ejection Fraction in PARADIGM-HF.

BACKGROUND: Hypotension is an important clinical problem in heart failure (HF). OBJECTIVES: This study sought to examine the association between asymptomatic vs symptomatic hypotension and outcomes in PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). METHODS: In a post hoc analysis of PARADIGM-HF, the efficacy and safety of sacubitril/valsartan compared to enalapril were estimated using time-updated Cox proportional hazards models. The primary outcome was cardiovascular death or HF hospitalization. RESULTS: Among 8,399 patients in PARADIGM-HF, 1,343 (16.0%) experienced only asymptomatic hypotension, and 936 (11.1%) experienced symptomatic hypotension at least once after randomization. Patients with symptomatic hypotension were older and more frequently had cardiovascular comorbidities compared to those developing only asymptomatic hypotension. By contrast, left ventricular ejection fraction was lower in those with asymptomatic hypotension. Patients who experienced either type of hypotension were at higher risk for all outcomes examined. However, the effect of sacubitril/valsartan on the primary outcome was not diminished in patients experiencing hypotension compared to those who did not: the HR for sacubitril/valsartan vs enalapril was 0.80 (95% CI: 0.72-0.89) for no hypotension, 0.87 (95% CI: 0.70-1.08) for asymptomatic hypotension, and 0.51 (95% CI: 0.38-0.69) for symptomatic hypotension (Pinteraction = 0.01), and this was also true for cardiovascular and all-cause deaths. The safety of sacubitril/valsartan vs enalapril was also maintained regardless of the occurrence of hypotension. Discontinuation of randomized treatment was less common with sacubitril/valsartan vs enalapril in patients experiencing asymptomatic and symptomatic hypotension. CONCLUSIONS: Although both asymptomatic and symptomatic hypotension during treatment with sacubitril/valsartan or enalapril were associated with worse outcomes, the benefits of sacubitril/valsartan were maintained (or even enhanced) in patients experiencing hypotension.

A prospective randomized controlled study of multi-intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure and reduced ejection fraction (PRIME-HFrEF) trial: Rationale and design.

Background and objective: The use of mesenchymal stem cells for heart failure treatment has gained increasing interest. However, most studies have relied on a single injection approach, with no research yet confirming the effects of multiple administrations. The present trial aims to investigate the safety and efficacy of multi-intravenous infusion of umbilical cord-mesenchymal stem cells (UC-MSCs) in patients with heart failure and reduced ejection fraction (HFrEF). Methods: The PRIME-HFrEF trial is a single-center, prospective, randomized, triple-blinded, placebo-controlled trial of multi-intravenous infusion of UC-MSCs in HFrEF patients. A total of 40 patients meeting the inclusion criteria for HFrEF were enrolled and randomized 1:1 to the MSC group or the placebo group. Patients enrolled will receive intravenous injections of either UC-MSCs or placebo every 6 weeks for three times. Both groups will be followed up for 12 months. The primary safety endpoint is the incidence of serious adverse events. The primary efficacy endpoint is a change in left ventricular ejection fraction (LVEF) measured by left ventricular opacification (LVO) with contrast echocardiography and magnetic resonance imaging (MRI) at 12 months. The secondary endpoints include a composite of the incidence of death and re-hospitalization caused by heart failure at the 12th month, serum NT-proBNP, growth stimulation expressed gene 2 (ST2), and a change of right ventricular structure and function. Conclusions: The PRIME-HFrEF study is designed to shed new light on multiple UC-MSC administration regimens for heart failure treatment.

Assessing the early prognosis of heart failure after acute myocardial infarction using left ventricular pressure-strain loop: a prospective randomized controlled clinical study.

Background: The left ventricular pressure-strain loop (LV-PSL) technique, which is noninvasive and independent of pressure load, is more sensitive than is left ventricular speckle tracking imaging in detecting subtle changes in myocardial function. This study evaluated the improvement in cardiac function after application of LV-PSL in patients with heart failure with reduced ejection fraction (HFrEF) after acute myocardial infarction (MI) treated with sacubitril/valsartan plus dapagliflozin as compared to treatment with sacubitril/valsartan monotherapy. Methods: This prospective, multicenter, open-label study recruited 60 MI survivors with HFrEF between March 2021 and June 2022. The patients were randomly assigned in 1:1 groups, as stratified by center. Patients were randomly categorized into either an observation group [n=30; conventional treatment + 100 mg (49/51 mg) of sacubitril/valsartan, + 10 mg of dapagliflozin] or a control group [n=30; conventional treatment + 100 mg (49/51 mg) of sacubitril/valsartan]. Patients were assessed at three time points: 1 month after discharge (T1), 3 months after discharge (T3), and 6 months after discharge (T6). Two-dimensional ultrasound images were routinely collected, two-dimensional speckle tracking imaging was applied to calculate the left ventricular global longitudinal strain (LV-GLS) rate for both groups, and LV-PSL analysis was used for the assessment of myocardial work, including global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. The results at the three follow-up visits were compared with the predischarge results (baseline, T0). Results: Compared with the values at T0, the LV-GLS and left ventricular myocardial work index (LVMWI) values increased in both the observation and control groups at T1, T3, and T6, with GWI and GCW showing significantly greater improvement in the observation group at T6 (GWI: 1,204±336 vs. 987±417 mmHg%, P=0.03; GCW: 1,401±348 vs. 1,206±356 mmHg%, P=0.04). Survival analysis revealed that the overall incidence of major adverse cardiovascular events (MACEs) in the observation group was significantly lower than that in the control group (P=0.03). In a multivariate logistic regression analysis including GCW, GWI, GLS, and left ventricular eject fraction (LVEF), GCW emerged as the only independent predictor of occurrence of MACEs (odds ratio =1.08; 95% CI: 0.63-0.93; P<0.001). Conclusions: Sacubitril/valsartan and dapagliflozin combination therapy led to a moderate improvement of cardiac function in patients with post-MI heart failure (P-MI-HF) compared to treatment with sacubitril/valsartan alone. Moreover, LV-PSL analysis can be used to assess the early prognosis of patients with P-MI-HF.

Ventricular remodeling and hemodynamic changes in heart failure patients with non-ischemic dilated cardiomyopathy following dapagliflozin initiation.

BACKGROUND: In heart failure with reduced ejection fraction (HFrEF), sodium-glucose co-transporter inhibitors (SGLT-2i) have persistently shown cardiovascular benefits through different trials. However, their impact on ventricular remodeling and cardiac hemodynamics has not been sufficiently studied. This study aimed to study how SGLT-2i initiation affects invasive hemodynamics and cardiac magnetic resonance imaging (CMR)-derived ventricular volumes, function, and fraction of the extracellular volume (ECV) in HFrEF patients with non-ischemic dilated cardiomyopathy (NIDCM). RESULTS: In this study, 23 patients with HFrEF and a mean age of 42, including 82.6% males, all have NIDCM and underwent right heart catheterization and CMR at the initiation of dapagliflozin and at 6-month follow-up. The addition of dapagliflozin resulted in significant reductions in the following invasive hemodynamic parameters compared to baseline: left ventricular end-diastolic pressure (23.4 vs 19.7 mmHg, p = 0.003), mean pulmonary artery pressure (31.3 vs 27.7 mmHg, p = 0.03), and systemic vascular resistance (18 vs 15 Wood units, p = 0.047). Among the studied CMR-derived measurements, only the percentage of extracellular volume fraction was significantly less at follow-up (33.7 vs 32.16%, p = 0.001). Additionally, functional class showed significant improvement with a notable reduction of the NT-proBNP level and a considerable decrease in diuretic dose (median: 40 vs 80 mg, p = 0.01). CONCLUSION: Adding dapagliflozin to patients with HFrEF due to NIDCM improved invasively measured hemodynamics and significantly reduced left ventricular extracellular volume fraction measured by CMR, with no significant change in ventricular volumes or ejection fraction.

Heart Failure With Improved Ejection Fraction: Prevalence, Predictors, and Guideline-Directed Medical Therapy.

Recently, a new category of heart failure with improved ejection fraction (HFimpEF) has emerged in the classification system. This is defined as the subgroup of patients with heart failure with reduced ejection fraction (HFrEF) whose left ventricular ejection fraction has recovered partially or completely, with no specific cut-off values established yet in the guidelines. In our review, we aim to provide an overview of prevalence, predictors, mechanism of remodeling, and management strategies regarding HFimpEF. These patients constitute a sizeable cohort among patients with reduced ejection fraction. Certain patient characteristics including younger age and female gender, absence of comorbid conditions, low levels of biomarkers, and non-ischemic etiology were identified as positive predictors. The heart undergoes significant maladaptive changes post failure leading to adverse remodeling influenced etiology and duration. Goal-directed medical therapy including beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin II receptor blockers (ARBs) have notably improved cardiac function by inducing reverse remodeling. Despite a more favorable prognosis compared to HFrEF, patients with improved ejection fraction (EF) still face clinical events and reduced quality of life, and remain at risk of adverse outcomes. Although the evidence is scarce, it is advisable to continue treatment modalities despite improvement in EF, including device therapies, to prevent relapse and clinical deterioration. It is imperative to conduct further research to understand the mechanism leading to EF amelioration and establish guidelines to identify and direct management strategies.