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.

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.

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.

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.

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.

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.

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.

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.

On- vs. Off-Pump CABG in Heart Failure Patients with Reduced Ejection Fraction (HFrEF): A Multicenter Analysis.

OBJECTIVE: This study aimed to compare postoperative outcomes and 30-day mortality in patients with reduced ejection fraction (<40%) who underwent isolated coronary artery bypass grafting (CABG) with (ONCAB) and without (OPCAB) the use of cardiopulmonary bypass. METHODS: data from four university hospitals in Germany, spanning from January 2017 to December 2021, were retrospectively analyzed. A total of 551 patients were included in the study, and various demographic, intraoperative, and postoperative data were compared. RESULTS: demographic parameters did not exhibit any differences. However, the OPCAB group displayed notably higher rates of preoperative renal insufficiency, urgent surgeries, and elevated EuroScore II and STS score. During surgery, the ONCAB group showed a significantly higher rate of complete revascularization, whereas the OPCAB group required fewer intraoperative transfusions. No disparities were observed in 30-day/in-hospital mortality for the entire cohort and the matched population between the two groups. Subsequent to surgery, the OPCAB group demonstrated significantly shorter mechanical ventilation times, reduced stays in the intensive care unit, and lower occurrences of ECLS therapy, acute kidney injury, delirium, and sepsis. CONCLUSIONS: the study's findings indicate that OPCAB surgery presents a safe and viable alternative, yielding improved postoperative outcomes in this specific patient population compared to ONCAB surgery. Despite comparable 30-day/in-hospital mortality rates, OPCAB patients enjoyed advantages such as decreased mechanical ventilation durations, shorter ICU stays, and reduced incidences of ECLS therapy, acute kidney injury, delirium, and sepsis. These results underscore the potential benefits of employing OPCAB as a treatment approach for patients with coronary heart disease and reduced ejection fraction.

Adherence to drug therapy in patients with heart failure associated with reduced ejection fractions (HFrEF) during cardiac rehabilitation and after 3 and 6 months.

INTRODUCTION: Heart failure represents a major challenge for healthcare systems worldwide. Rehabilitation is recommended as an important pillar of therapy for these patients, especially for those with reduced left ventricular ejection fraction (HFrEF: heart failure with reduced ejection fraction). METHODS: The data collected in this multi-center project provide information on the rates of patients with HFrEF who were treated in five German rehabilitation facilities and whether the patients adhered to drug therapy at 3-/6-month follow-up. The project was supported by an unrestricted grant from Novartis-Pharma-GmbH. RESULTS: The mean age of the 234 patients included was 63.4 ± 10.6 years and 78% were male. The mean LVEF was 31 ± 8% at admission and 36 ± 10% at discharge. Only 20.6% of the patients were assigned to rehabilitation with the main indication HF. The most frequent main indication was acute coronary syndrome (46.6%). A high proportion of patients was already on the recommended drug therapy upon admission (94% beta blockers, 100% angiotensin-effective drugs, 70% mineralocorticoid receptor antagonists, etc.). This was optimized, in particular by a higher proportion of patients treated with sodium-glucose cotransporter-2 inhibitors (35% admission vs. 45% discharge) and sacubitril/valsartan (49% admission vs. 64% discharge), which was further optimized during the 6-month follow-up (e.g., 50% SGLT2 inhibitors, 67% sacubitril/valsartan). DISCUSSION: These data illustrate the effect of rehabilitation in terms of optimizing drug therapy, which stabilized over the course of 6 months. Furthermore, only a few patients with the main diagnosis HFrEF are referred for cardiac rehabilitation, although it is an essential part of guideline-based therapy.

The Long-Term Benefit of Sacubitril/Valsartan in Patients with HFrEF: A 5-Year Follow-Up Study in a Real World Population.

Heart failure (HF) is a progressive condition with an increasing prevalence, and the scientific evidence of heart failure with reduced ejection fraction (HFrEF) reports a 6% rate of 1-year mortality in stable patients, whereas, in recently hospitalized patients, the 1-year mortality rates exceed 20%. The Sacubitril/Valsartan (S/V), the first angiotensin receptor neprilysin inhibitor (ARNI), significantly reduced both HF hospitalization and cardiovascular mortality. AIM OF THE STUDY: to evaluate the effect of S/V in a follow-up period of 5 years from the beginning of the therapy. We compared the one-year outcomes of S/V use with those obtained after 5 years of therapy, monitoring the long-term effects in a real-world population with HFrEF. METHODS: Seventy consecutive patients with HFrEF and eligible for ARNI, according to PARADIGM-HF criteria, were enrolled. All patients had an overall follow-up of 60 months, during which time they underwent standard transthoracic echocardiography (TTE) with Global Longitudinal Strain (GLS) evaluation, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Six Minutes Walking Test (6MWT), and blood tests (NT-pro-BNP and BNP, renal function tests). RESULTS: NTproBNP values were reduced significantly among the three time-points (p < 0.001). Among echocardiographic parameters, left ventricle end-diastolic volume (LV EDV) and E/e' significantly were reduced at the first evaluation (12 months), while left ventricle end-systolic volume (LV ESV) decreased during all follow-ups (p < 0.001). LV EF (p < 0.001) and GLS (p < 0.001) significantly increased at both evaluations. The 6MWT (p < 0.001) and KCCQ scores (p < 0.001) increased significantly in the first 12 months and remained stable along the other time-points. NYHA class showed an increase in class 1 subjects and a decrease in class 3 subjects during follow-up. NTproBNP, BNP, 6MWT, and KCCQ scores showed a significant change in the first 12 months, while LVEF, GLS, and ESV changed during all evaluations. CONCLUSIONS: We verified that the improvements obtained after one year of therapy had not reached a plateau phase but continued to improve and were statistically significant at 5 years. Although our data should be confirmed in larger and multicentre studies, we can state that the utilization of Sacubitril/Valsartan has catalysed substantial transformations in the prognostic landscape of chronic HFrEF, yielding profound clinical implications.

Penalized Model-Based Unsupervised Phenomapping Unravels Distinctive HFrEF Phenotypes With Improved Outcomes Discrimination From Sacubitril/Valsartan Treatment Independent of MAGGIC Score.

Background The angiotensin receptor-neprilysin inhibitor (LCZ696) has emerged as a promising pharmacological intervention against renin-angiotensin system inhibitor in reduced ejection fraction heart failure (HFrEF). Whether the therapeutic benefits may vary among heterogeneous HFrEF subgroups remains unknown. Methods and Results This study comprised a pooled 2-center analysis including 1103 patients with symptomatic HFrEF with LCZ696 use and another 1103 independent HFrEF control cohort (with renin-angiotensin system inhibitor use) matched for age, sex, left ventricular ejection fraction, and comorbidity conditions. Three main distinct phenogroup clusterings were identified from unsupervised machine learning using 29 clinical variables: phenogroup 1 (youngest, relatively lower diabetes prevalence, highest glomerular filtration rate with largest left ventricular size and left ventricular wall stress); phenogroup 2 (oldest, lean, highest diabetes and vascular diseases prevalence, lowest highest glomerular filtration rate with smallest left ventricular size and mass), and phenogroup 3 (lowest clinical comorbidity with largest left ventricular mass and highest hypertrophy prevalence). During the median 1.74-year follow-up, phenogroup assignment provided improved prognostic discrimination beyond Meta-Analysis Global Group in Chronic Heart Failure risk score risk score (all net reclassification index P<0.05) with overall good calibrations. While phenogroup 1 showed overall best clinical outcomes, phenogroup 2 demonstrated highest cardiovascular death and worst renal end point, with phenogroup 3 having the highest all-cause death rate and HF hospitalization among groups, respectively. These findings were broadly consistent when compared with the renin-angiotensin system inhibitor control as reference group. Conclusions Phenomapping provided novel insights on unique characteristics and cardiac features among patients with HFrEF with sacubitril/valsartan treatment. These findings further showed potentiality in identifying potential sacubitril/valsartan responders and nonresponders with improved outcome discrimination among patients with HFrEF beyond clinical scoring.

The Utility of Low-Dose-Dobutamine Stress Echocardiography in Patients with Heart Failure with Reduced Ejection Fraction: An Update.

Despite significant advancements in medical therapy, heart failure with reduced ejection fraction (HFrEF) continues to be a significant cause of death and disability. Reversible ischaemic left ventricular dysfunction due to viable myocardium is one such contributing factor. In these cases, coronary revascularization has shown promise in improving left ventricular function and prognosis. For patients with HFrEF and wide QRS, cardiac resynchronization therapy (CRT) is an effective option to address electromechanical dyssynchrony. However, approximately 30% of patients do not respond positively to CRT, highlighting the need to refine candidate selection for this treatment. In some patients with reduced HFrEF, there is a condition known as classical low-flow, low-gradient aortic stenosis (AS) that may be observed. This condition is characterized by a low transaortic flow, which leads to reductions in both the transaortic mean gradient and aortic valve area. Decision-making regarding revascularization, CRT, and pharmacological treatment play a crucial role in managing HFrEF. Cardiac imaging can be valuable in guiding decision-making processes and assessing the prognosis of patients with HFrEF. Among the imaging modalities, dobutamine stress echocardiography has come a long way in establishing itself as a feasible, safe, effective, relatively cheap non-invasive technique. The aim of this review is to explore the current literature on the utility of low-dose stress echocardiography in diagnosing and prognosticating patients with HFrEF.

Telmisartan versus EnalapRil In heart failure with redUced ejection fraction patients with Moderately impaired kidney Functions; randomized controlled trial: "TRIUMF trial".

BACKGROUND: When heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) co-exist, Renin angiotensin-aldosterone system inhibitors (RAASi) are often underutilized for the fear of worsening renal function (WRF). Telmisartan is a RAASi characteristic for a favorable renal profile, although data on its utility in HFrEF is limited. This study aimed to compare efficacy and tolerability of Telmisartan versus Enalapril in patients with HFrEF and CKD. RESULTS: This study randomized 107 patients with HFrEF and CKD to either Telmisartan (10-80 mg) or Enalapril (5-40 mg) daily. The achieved RAASi dose, dose reductions (DR) or dis-continuation (DC), death/Heart failure rehospitalization (HFH), NYHA class and 6MWT were compared at 3- and 6-months. At 3- and 6-months, 93.5% versus 68.6% and 95.2% versus 72.9% were maintaining ≥ 50% of the target dose in the Telmisartan- versus Enalapril-group, respectively. Despite the higher achieved dose by 3- and 6-months, Telmisartan versus Enalapril was associated with less WRF (6.4% vs. 22.9%, p = 0.022 and 7.3% vs. 13.6%, p = 0.28) and fewer episodes of DR-DC (31.9% vs. 55.1%, p = 0.018 and 35.7% vs. 56.5%, p = 0.041), respectively. By the end of the study, there were 5 deaths in each group, yet, HFH occurred in 34.1% versus 55.3%, p = 0.035, and NYHA class changed by - 1 [- 2, 0] versus 0 [- 1, 1], p = 0.017 in Telmisartan- versus Enalapril patients, respectively. Within-group results showed improvement in 6MWT in Telmisartan-, and increase in diuretic requirements in Enalapril-group. CONCLUSIONS: In patients with HFrEF and CKD, Telmisartan was better tolerated to uptitrate, caused less WRF, less HFH and showed better functional improvement compared to Enalapril. Clinical trial registration This study was prospectively registered on clinicaltrials.gov, with registration number (NCT04736329).

Mini review: The clinical avenues of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction

Background: Combined hydralazine-nitrate has an avenue in the management of subjects with heart failure with reduced ejection fraction. Exploring the pharmacotherapy in this context will facilitate the clinical utility of the combined therapy. Objective: The main objective of this mini-review was to evaluate the role of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction. Methods: We conducted a literature search on Google scholar, MEDLINE, and PubMed to identify the randomized clinical trials on combined hydralazine-nitrate, in subjects with heart failure with reduced ejection fraction. 2760 articles were returned initially out of which 10 trials were conforming to the inclusion criteria. However, three trails were the focus for the current mini-review. Key findings: The current mini-review lends support to the use of combined hydralazine-nitrate in subjects with heart failure with reduced ejection fraction (HFrEF). The combination may offer subjects who have remained symptomatic with HFrEF despite optimum dosing of standard therapy. Black subjects with HFrEF have proved to benefit from combined hydralazine-nitrate. The combination (e.g. small dose of hydralazine 12.5-25 mg twice a day and isosorbide mononitrate 10 mg twice a day) may provide alternative clinical utility in subjects with contraindications (renal artery stenosis, creatinine clearance less than 30 mL/minute, sustained hyperkalemia) to the use of ACEinh, ARBs, and/or ARNI. Subjects with HFrEF on combined hydralazine-nitrate should be assessed and monitored for systolic BP (keep >120 mmHg) and subjects with chronic kidney disease (keep eGFR > 30 mL/min/1.73 m2). Hydralazine-nitrate was inferior to ACEinh (higher all-cause mortality and cardiovascular mortality. Conclusion: The current mini- review provides the key points to support the use of hydralazine-nitrate in subjects with heart failure with reduced ejection fraction. (AU)

Polypharmacy and Optimization of Guideline-Directed Medical Therapy in Heart Failure: The GUIDE-IT Trial.

BACKGROUND: Polypharmacy is common among patients with heart failure with reduced ejection fraction (HFrEF). However, its impact on the use of optimal guideline-directed medical therapy (GDMT) is not well established. OBJECTIVES: This study sought to evaluate the association between polypharmacy and odds of receiving optimal GDMT over time among patients with HFrEF. METHODS: The authors conducted a post hoc analysis of the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial. Polypharmacy was defined as receiving ≥5 medications (excluding HFrEF GDMT) at baseline. The outcome of interest was optimal triple therapy GDMT (concurrent administration of a renin-angiotensin-aldosterone blocker and beta-blocker at 50% of the target dose and a mineralocorticoid receptor antagonist at any dose) achieved over the 12-month follow-up. Multivariable adjusted mixed-effect logistic regression models with multiplicative interaction terms (time × polypharmacy) were constructed to evaluate how polypharmacy at baseline modified the odds of achieving optimal GDMT on follow-up. RESULTS: The study included 891 participants with HFrEF. The median number of non-GDMT medications at baseline was 4 (IQR: 3-6), with 414 (46.5%) prescribed ≥5 and identified as being on polypharmacy. The proportion of participants who achieved optimal GDMT at the end of the 12-month follow-up was lower with vs without polypharmacy at baseline (15% vs 19%, respectively). In adjusted mixed models, the odds of achieving optimal GDMT over time were modified by baseline polypharmacy status (P for interaction < 0.001). Patients without polypharmacy at baseline had increased odds of achieving GDMT (OR: 1.16 [95% CI: 1.12-1.21] per 1-month increase; P < 0.001) but not patients with polypharmacy (OR: 1.01 [95% CI: 0.96-1.06)] per 1-month increase). CONCLUSIONS: Patients with HFrEF who are on non-GDMT polypharmacy have lower odds of achieving optimal GDMT on follow-up.

Heart failure with reduced ejection fraction and atrial fibrillation: a Sub-Saharan African perspective.

Cardiovascular diseases are a well-established cause of death in high-income countries. In the last 20 years, Sub-Saharan Africa (SSA) has seen one of the sharpest increases in cardiovascular disease-related mortality, superseding that of infectious diseases, including HIV/AIDS, in South Africa. This increase is evidenced by a growing burden of heart failure and atrial fibrillation (AF) risk factors. AF is a common comorbidity of heart failure with reduced ejection fraction (HFrEF), which predisposes to an increased risk of stroke, rehospitalizations, and mortality compared with patients in sinus rhythm. AF had the largest relative increase in cardiovascular disease burden between 1990 and 2010 in SSA and the second highest (106.4%) increase in disability-adjusted life-years (DALY) between 1990 and 2017. Over the last decade, significant advancements in the management of both HFrEF and AF have emerged. However, managing HFrEF/AF remains a clinical challenge for physicians, compounded by the suboptimal efficacy of guideline-mandated pharmacotherapy in this group of patients. There may be an essential role for racial differences and genetic influence on therapeutic outcomes of HFrEF/AF patients, further complicating our overall understanding of the disease and its pathophysiology. In SSA, the lack of accurate and up-to-date epidemiological data on this subgroup of patients presents a challenge in our quest to prevent and reduce adverse outcomes. This narrative review provides a contemporary overview of the epidemiology of HFrEF/AF in SSA. We highlight important differences in the demographic and aetiological profile and the management of this subpopulation, emphasizing what is currently known and, more importantly, what is still unknown about HFrEF/AF in SSA.

The clinical effect of sacubitril valsartan combined with dapagliflozin in heart failure with reduced ejection fraction and non-diabetes patients / 西安交通大学学报(医学版)

【Objective】 To observe the clinical effect of combination therapy of sacubitril valsartan and dapagliflozin in heart failure with reduced ejection fraction (HFrEF) and non-diabetes patients. 【Methods】 This study involved 96 patients with HFrEF and non-diabetes. The patients were randomly divided into control group (50 cases) and observation group (46 cases). On the basis of routine treatment, the control group was treated with sacubitril valsartan, while the observation group was treated with sacubitril valsartan and dapagliflozin. After 1-month and 6-month treatment, we monitored blood pressure, N-terminal pro brain natriuretic peptide (NT-proBNP), high sensitivity troponin T (cTnT), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left atrial diameter (LAD), left ventricular posterior wall thickness (LVPW), Minnesota soda heart failure life quality score (MLHFQ), the incidence of rehospitalization and death, and major adverse cardiovascular events (MACE) in the two groups. 【Results】 After 6 months, systolic blood pressure, cTnT, NT-proBNP, LVEDd, LVPW, and LAD of the observation group were significantly decreased compared with the control group (P0.05). 【Conclusion】 The combination treatment of sacubitril valsartan and dapagliflozin on HFrEF and non-diabetes patients can significantly improve cardiac function, inhibit myocardial remodeling, reduce the incidence of MACE, and improve the prognosis.

Reverse Remodeling Assessed by Left Atrial and Ventricular Strain Reflects Treatment Response to Sacubitril/Valsartan.

BACKGROUND: The left ventricular global longitudinal strain (LVGLS) and left atrial reservoir strain (LARS) are considered as sensitive and reliable markers of cardiac remodeling and function. However, their temporal changes during optimal management of heart failure with reduced ejection fraction (HFrEF) are unknown. OBJECTIVES: This study investigated the time trajectories of the LARS and LVGLS in patients with HFrEF treated with angiotensin receptor-neprilysin inhibitors, and assessed whether the LARS and LVGLS could define left heart reverse remodeling (LHRR) and reflect the treatment response and prognosis. METHODS: Using a retrospective cohort of patients with HFrEF prescribed sacubitril/valsartan, we assessed the time trajectories of the LVGLS and LARS in 409 patients (1,258 echocardiograms), and investigated their association with the occurrence of cardiovascular death and hospitalization for heart failure (HHF), after the determination of LHRR, during a median follow-up of 27.1 (IQR: 18.3-36.3) months. RESULTS: Among patients with HFrEF prescribed sacubitril/valsartan, both the LVGLS and LARS improved over time. The improvements in the LVGLS and LARS were prominent within 6 months of sacubitril/valsartan treatment: the LVGLS improved from 10.2% (IQR: 7.9%-12.7%) to 13.9% (IQR: 10.5%-16.3%) (P < 0.001), and the LARS improved from 11.4% (IQR: 8.4%-15.6%) to 15.9% (IQR: 11.5%-21.4%) (P < 0.001). These improvements were larger among patients who did not experience the study outcome than in patients with events. Improvement in the LVGLS to ≥13% and LARS to ≥12.5% (ie, complete LHRR) was significantly associated with a lower risk of cardiovascular death and HHF, and this association was stronger than that of changes in other conventional echocardiographic parameters. CONCLUSIONS: In patients with HFrEF treated with sacubitril/valsartan, the LVGLS and LARS were improved, typically within 6 months of treatment. Complete LHRR, defined by improvement in the LVGLS and LARS, can be an indicator of treatment response and prognosis.

Periodontal Status, C-Reactive Protein, NT-proBNP, and Incident Heart Failure: The ARIC Study.

BACKGROUND: Periodontal disease (PD), resulting from inflammatory host response to dysbiotic subgingival microbiota, has been linked to cardiovascular disease; however, its relationship to heart failure (HF) and its subtypes (heart failure with reduced ejection fraction [HFrEF] and heart failure with preserved ejection fraction [HFpEF]) is unexplored. OBJECTIVES: The authors hypothesize that the presence of PD is associated with increased risk of incident HF, HFpEF, and HFrEF. METHODS: A total of 6,707 participants (mean age 63 ± 6 years) of the ARIC (Atherosclerosis Risk In Communities) study with full-mouth periodontal examination at visit 4 (1996-1998) and longitudinal follow-up for any incident HF (visit 4 to 2018), or incident HFpEF and HFrEF (2005-2018) were included. Periodontal status was classified as follows: healthy, PD (as per Periodontal Profile Classification [PPC]), or edentulous. Multivariable-adjusted Cox proportional hazards models were used to calculate HRs and 95% CIs for the association between PPC levels and incident HF, HFpEF, or HFrEF. Additionally, biomarkers of inflammation (C-reactive protein [CRP]) and congestion (N-terminal brain natriuretic peptide [NT-proBNP]) were assessed. RESULTS: In total, 1,178 incident HF cases occurred (350 HFpEF, 319 HFrEF, and 509 HF of unknown type) over a median of 13 years. Of these cases, 59% had PD, whereas 18% were edentulous. PD was associated with an increased risk for HFpEF (HR: 1.35 [95% CI: 0.98-1.86]) and significantly increased risk for HFrEF (HR: 1.69 [95% CI: 1.18-2.43]), as was edentulism: HFpEF (HR: 2.00 [95% CI: 1.37-2.93]), HFrEF (HR: 2.19 [95% CI: 1.43-3.36]). Edentulism was associated with unfavorable change in CRP and NT-proBNP, whereas PD was associated only with CRP. CONCLUSIONS: Periodontal status was associated with incident HF, HFpEF, and HFrEF, as well as unfavorable changes in CRP and NT-proBNP.