Medical Therapy For Heart Failure Research Articles

Mechanisms affecting the neutrophil to lymphocyte ratio in heart failure: a prospective CMR study

Abstract Background The neutrophil-to-lymphocyte ratio (NLR) is a simple measure of inflammation defined as the ratio of the neutrophils to lymphocytes as measured in the full blood count. It is well known that patients with heart failure (HF) have elevated levels of pro-inflammatory cytokines. It has been demonstrated in a recent meta-analysis that elevated NLR in heart failure is significantly associated with worse outcomes including all-cause mortality, heart failure readmissions and cardiovascular death. Purpose Given this association between NLR and adverse prognosis in HF, we aim to identify which factors are associated with an elevated NLR. This may help to recognise patients at higher risk and guide management. Methods Patients with newly diagnosed HF and left ventricular ejection fraction <50% on referral echocardiogram were prospectively recruited at the time of referral for cardiovascular magnetic resonance (CMR). Exclusion criteria included prior revascularisation, myocardial infarction, anginal chest pain, congenital heart disease and suspected myocarditis. In one appointment patients (N=599) underwent clinical assessment, medication review, full blood count and CMR. The CMR protocol included quantitative assessment myocardial blood flow at stress and rest, assessment of ischaemic and non-ischaemic fibrosis by late gadolinium enhancement imaging and T1 and T2 mapping. Guideline directed medical therapy was determined by the referring physician. Baseline demographic data, medication and MRI results were recorded for all patients. NLR was calculated from full blood count and split into tertiles. Clinical and CMR parameters were compared between tertiles by analysis of variance and chi squared test. Results See Table 1 The factors which were found to be significantly associated with an elevated NLR were age, atrial fibrillation, NTproBNP, diuretic dose, inducible ischaemia and ischaemic fibrosis. Of note there was no significant difference between groups in terms of guideline directed medical therapy use or other CMR parameters. Conclusion NLR is increasingly recognised as a marker of adverse risk in patients with heart failure. This prospective study of 599 heart failure patients with reduced ejection fraction has identified that an elevated NLR is associated with: 1. Evidence of congestion as evidenced by NTproBNP results and increased diuretic doses. 2. Occult coronary artery disease as shown by greater levels of inducible ischaemia and ischaemic fibrosis. These findings suggest that the adverse prognosis associated with elevated NLR in heart failure may be mediated by worsening congestion and occult coronary artery disease. Importantly there was no association between myocardial inflammation or oedema (measured as native T1 and T2) and NLR. Whether NLR improves with medical therapy of heart failure remains to be established and our findings need to be validated in more varied cohorts of patients with heart failure.

Secondary erythrocytosis / polycythemia due to sodium glucose co-transporter 2 inhibitors: a real world heart failure cohort

Abstract Background Sodium glucose co-transporter 2 inhibitors (SGLT2-i) are one of the four pillars of guideline-directed medical therapy in heart failure with reduced ejection fraction and preserved ejection fraction according to the current ESC and AHA/ACC heart failure guidelines 1,2. As a result, there has been a significant increase in their use worldwide. Although SGLT2 inhibitors are known to increase hemoglobin and hematocrit levels, there is a lack of data on the burden of erythrocytosis or polycythemia in pivotal trials 3,4. Purpose In this retrospective cohort study, we investigated the prevalence and clinical outcomes of SGLT2-i related erythrocytosis in a tertiary heart failure outpatient clinic. Methods We reviewed clinical data from heart failure patients treated with an SGLT2 inhibitor at our tertiary centre between September 2019 and October 2023. Patients were included if they were taking SGLT2-i continuously for more than one month. Data were collected on Hb/Hct levels at baseline before initiation of SGLT2-i, at peak levels during therapy and at the last follow-up. Erythrocytosis was defined according to the 2017 WHO classification as Hb> 10.3 mmol/L and/or Hct> 49% in men and Hb> 10.0 mmol/L and/or Hct> 48% in females. Results A total of 173 patients with heart failure were included (median age 58 [49-66] years, 65% male). One hundred and fifty-six patients (90%) were using dapagliflozin, while 16 patients (9%) were using empagliflozin. The overall prevalence of SGLT2i related erythrocytosis was 39/173 (22.5%; median age 60 and 82% males). Eleven (6.3%) patients had pre-existing erythrocytosis at baseline. During a mean follow-up of 14±10 months, 28/173 (16.2%) patients developed new onset erythrocytosis. The median time to the peak of the Hb/Hct level was 6.5 months. Although the group with erythrocytosis had significantly higher Hb and Hct at baseline compared to the group without erythrocytosis (Hb 9.7 mmol/L ± 1.0 vs. 8.5 mmol/L ± 1.0; p<0.001 in men and 9.1 mmol/L ± 0.8 mmol/L vs. 8.1 ± 0.8; p=0.006 in females), they also experienced a significantly greater median increase in Hb from baseline to peak (1.05 mmol/L vs. 0.60mmol/L; p=0.01) (see Figure 1) There were significantly more males (82% vs 60%; p=0.01) in the erythrocytosis group compared to the non-erythrocytosis group. In addition, the prevalence of OSAS was significantly higher in the group with erythrocytosis compared to the group without erythrocytosis (31% vs. 8%; p<0.001). Conclusion Secondary erythrocytosis or polycythemia is common in patients with chronic heart failure. It is particularly common in men and in patients with obstructive sleep apnoea syndrome (OSAS). There were no excess thrombotic or thromboembolic events, probably because of the routine use of anticoagulants/antiplatelets and limited follow-up. To avoid unnecessary haematological referrals and potential clinical adverse events, increased awareness among clinicians is needed.Table 1.Baseline and clinical outcomesFig1.Hemoglobin levels over time

Utilization and safety of digoxin in patients with chronic heart failure and atrial fibrillation with rapid ventricular rate

Abstract Background Digoxin can reduce symptoms and the risk of tachycardia-induced cardiomyopathy in patients with heart failure (HF) and concomitant atrial fibrillation (AF) with rapid ventricular rate. The effect of digoxin in HF and AF has not been tested in randomized controlled trials, and observational data have shown conflicting results linking digoxin to increased mortality in AF, though the nature of observational data makes it prone to bias and results difficult to interpret. Purpose To assess the utilization of digoxin in patients with HF and AF, and its association with New York Heart Association (NYHA) functional class and survival. Methods We used data from the Norwegian HF registry that collected data from all Norwegian HF clinics between 2013-2022. Data was collected from the first and last visit during optimizization of HF medical therapy. Associations with mortality status from Statistics Norway were assessed in unadjusted time-to-event analysis, and after adjustment for age, sex, body mass index, estimated glomerular filtration rate, aldosterone antagonists, renin-angiotensin-aldosterone system inhibitors, and beta blockers. Results The study included 4,877 HF patients, consisting of 4,067 (83.4%) with ejection fraction (EF) ≤40% and 810 (16.6%) with EF >40%.. The mean age was 67.7±12.0 years; 25.1% were women, and 27.3% had NYHA functional class III/IV. At the first visit, 1,339 (27.5%) patients had AF and 829 (61.9%) of these were treated with ≥50% of the beta-blocker target dose. AF with a ventricular rate ≥100 bpm was present in 277 (20.1%) patients, and 188 (67.9%) of these were on ≥50% beta-blocker target dose. Similarly, 262 (19.6%) of all AF patients and 44 (15.9%) of those with a ventricular rate ≥100 bpm were treated with digoxin. After optimization of HF medical therapy (median duration 140 [Q1–Q3 82–237] days), 1,039 (21.3%) patients had AF. Among these, 227 (21.9%) were treated with digoxin, including 9 (18.0%) patients with ventricular rate ≥100 bpm. Patients with AF who were started on digoxin experienced during the optimization period a larger decline in heart rate compared to those who were not (mean change -23.7±17.2 vs. -5.7±16.7 bpm, p=0.001), and more often an improvement in NYHA functional class (45% vs 30%, p=0.018). During median 779 [Q1–Q3 386–1,334)] days of follow-up after the last optimization visit, digoxin use was associated with lower mortality in HF patients with AF in unadjusted analysis (HR 0.67 [0.46–0.97]). After adjustment for baseline characteristics and other HF medical therapies, the association with mortality was attenuated and no longer significant (HR 0.96 [0.65–1.42]). Conclusion Digoxin was infrequently used in patients with HF and AF with rapid ventricular rate but was associated with a greater decrease in heart rate and improvement in NYHA functional class. The use of digoxin appears safe and was not associated with increased mortality.

ICARUS registry: findings from the first 1595 cases of acute decompensated heart failure in a single center in a latin american country

Abstract Introduction Institutional aCute decompensAted HeaRt FailUre RegiStry (ICARUS) will provide information on clinical characteristics, medical practice, patterns of treatment, and outcomes of patients hospitalized with Acute Decompensated Heart Failure (ADHF) in a hospital in a middle-income country. Objective Describe the methodological aspects, sociodemographic, and clinical characteristics of patients hospitalized with ADHF and their short-term outcomes. Method Prospective cohort of patients with ADHF from the emergency service of a cardiovascular center. Descriptive statistics were used to synthesize sociodemographic characteristics, clinical characteristics during hospitalization, and outcomes. Results 1595 patients with ADHF. The median age was 68 years (Q1=58; Q3=76), and 69.28% were men. The median hospital stay was six days (Q1=4; Q3=11), with an accumulative incidence (AI) for rehospitalization at 30 days of 8.70 % (95% CI 7.18 to 10.40%), in-hospital mortality AI of 4.33% (95% CI 3.38 to 5.44%), and a median change in the quality-of-life score like Minnesota Living with Heart Failure Questionnaire (MLHFQ) at 30 days of -20 points (Q1=-37; Q3=-5). At discharge, all patients had a percentage greater than 70% of the use of quadruple neurohormonal blockade therapy. Conclusions ICARUS is one of the first registries in Latin America since the indication of the use of SGLT2 inhibitors, evaluating the clinical and sociodemographic characteristics, treatment patterns, and outcomes of a preliminary cohort of 1595 patients hospitalized for ADHF. The results indicate that, at discharge, up to 82.79% of patients were receiving quadruple neurohormonal blockade therapy, which is considerably challenging to achieve in Latin America. Considering the results of the Safety, tolerability and efficacy of up-titration of Guideline-Directed Medical therapies for acute heart failure (STRONG-HF study), our study reinforces the benefit of discharge with Guideline-Directed Medical Therapy (GDMT) for heart failure from hospitalization. The use of GDMT for heart failure may have influenced our positive outcomes in terms of in-hospital mortality, improvement in quality of life, and the percentage of short-term rehospitalizations compared to similar cohorts.Proportion of HF drug group

The impact of comorbidities on therapy-optimization and their prognostics role among hospitalized patients with heart failure with reduced ejection fraction

Abstract Background The early, accurate diagnosis and proper treatment of comorbidities (CMs) are of strategic importance in heart failure (HF), as stated in the current ESC HF Guidelines. Unquestionably, the presence of CMs is associated with worse prognosis. Moreover, CMs can unfavourably affect the implementation of the guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). Aim To assess the prevalence of the relevant prognosis-modifying CMs among patients requiring hospitalization due to HFrEF, investigate their effect on the implementation and optimization of GDMT, and examine the impact of the presence of CMs on the prognosis in HFrEF. Patients and methods The data of 313 patients requiring hospitalization at our Institution due to HFrEF between 2021-2023 (male: 77%, age: 60[50-70]years, coronary artery disease: 46%, diabetes: 36%, hypertension: 65%, atrial fibrillation: 42%, LVEF: 24[20-30]%, eGFR at admission: 57[46-74]mL/min/1.73m², NT-proBNP at admission: 5035[2376-9369]pg/mL, SBP: 121[110-140]mmHg; GDMT at admission - RASi[ACEi/ARB/ARNI]: 60%, βB: 59%, MRA: 44%, SGLT2i: 14%) were analyzed retrospectively. Based on the number of diagnosed CMs, patients were divided into 3 categories: 0-1 vs. 2-3 vs. ≥4 CMs. The implemented GDMT at discharge was compared among CM categories with Chi-square test, while all-cause mortality (ACM) rates were investigated with Kaplan-Meier method and multivariate Cox-regression analysis. Results During the hospitalization in the total cohort the proportion of patients on GDMT increased significantly (RASi: 91%, βB: 85%, MRA: 96%, SGLT2i: 57%; patients on triple [TT] therapy [RASi+βB+MRA]: 83%, patients on quadruple therapy [TT+SGLT2i]: 52%; p＜0.05). However, among patients with higher rates of CMs, the application of GDMT was less favourable (RASi: 97% vs. 94% vs. 82%; βB: 93% vs. 89% vs. 75%; p＜0.05; 0-1 vs. 2-3 vs. ≥4 CMs), the proportion of patients on TT and QT remained remarkably high even among those with ≥4 CMs (TT: 93% vs. 87% vs. 71%; QT: 65% vs. 52% vs. 45%; p＜0.05). During the median follow-up period of 1.3 year, the ACM of patients with increased burden of CMs was higher (12% vs. 18% vs. 37%, p＜0.001). According to the results of the multivariate Cox-regression analysis, more advanced left ventricular systolic dysfunction (/1%), previously confirmed diagnosis of HFrEF, the growing number of CMs proved to be negative independent predictors of ACM, while the application of TT or QT reduced the risk of ACM significantly (HR: 0.471, 95% CI: 0.271-0.819, p=0.008). Conclusions According to our real-world analysis, although among HFrEF patients with an increased burden of CMs, less favourable prognosis can be expected, the application of modern GDMT is even possible among them, resulting in a significantly improved prognosis. Thus, clinicians should insist on the early, conscious implementation of GDMT among these patients as well.

Temporal trends in sudden cardiac death after acute decompensation in HFrEF patients: a 13-year Japanese multicentre registry study

Abstract Background The implementation of guideline-based medical therapy (GBMT) for heart failure with reduced ejection fraction (HFrEF) has significantly contributed to reducing mortality risks. Yet, detailed analyses on temporal trends of sudden cardiac death (SCD) among these patients, especially post-discharge following acute decompensation, remain scarce. Purpose This study aimed to explore changes in the incidence of SCD over the last 13 years in patients with HFrEF discharged after acute decompensation treatment, and to identify clinical factors associated with SCD risk. Methods We analyzed 2,604 consecutive HFrEF (left ventricular ejection fraction [LVEF] ≤40%) patients enrolled in a Japanese multicentre acute heart failure (HF) registry from 2009 to 2021. SCD was defined as an unexpected and otherwise unexplained death in a previously stable patient or death due to documented or presumed cardiac arrhythmia without a clear non-cardiovascular cause. The determination of death cause (SCD, pump failure death, or other) was made by a central adjudicating committee. The Fine and Gray method was employed to analyze factors associated with SCD. The variables submitted to the model included age (≥70 years), gender, LVEF (<30%), ischaemic aetiology and prescription of GBMT (use of renin-angiotensin system inhibitors, β-blockers and mineralocorticoid receptor antagonist) at discharge. Results The mean age of studied patients was 70.9±14.2 years, and 70.0% were male. During the 1-year follow-up period, 262 deaths (10.1%) occurred, including 51 SCDs (2.0%). Older age was associated with an increased risk of SCD (adjusted hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.40-5.64, P=0.004). Further, patients with an ischaemic aetiology had a higher risk of SCD (HR 1.84, 95% CI 1.06-3.22, P=0.032). During the study period, mean age remained constant (71.0 years to 70.7 years, P for trend =0.884). The proportion of ischaemic aetiology also remained constant (from 37.2% to 38.2%, P for trend =0.972). Overall, there were significant decreases in the incidence of all cause death and SCD (from 13.7% to 8.4%, P for trend =0.002; and from 3.5% to 1.0%, P for trend <0.001; Figure A). Notably, there was an increase in the prescription rate of three classes of GBMT at discharge (from 30.9% to 45.6%, P for trend <0.001; Figure B), and the rate of implantable cardioverter-defibrillator (ICD) use in eligible patients (New York Heart Association functional class II-III with LVEF ≤35%) remained constant (from 9.6% to 11.6%, P for trend =0.157; Figure B). Conclusions With the increasing use of GBMT, the incidence of SCD decreased in real-world patients with HFrEF registered in a Japanese acute HF registry over the past decade.

Significant correlation between the extent of myocardial fibrosis and heart failure parameters in patients undergoing transcatheter aortic valve implantation

Abstract Background Recent studies have demonstrated that the prognosis of patients undergoing transcatheter aortic valve implantation (TAVI) is determined by the presence of myocardial fibrosis. The aim of this study was to quantify myocardial fibrosis in tissues obtained through myocardial biopsy before TAVI and to evaluate the relationship between the extent of myocardial fibrosis and baseline cardiac parameters. Methods We performed a retrospective single-center study, including 93 patients who underwent cardiac biopsies before TAVI from December 2022 to December 2023. The extent of myocardial fibrosis was assessed on Masson’s trichrome-stained tissue specimens, using a validated software "ImageJ". Results Median percent area of myocardial fibrosis in the entire cohort was 4.7% (interquartile range: 2.5 - 7.9). A significant correlation was found between the extent of myocardial fibrosis and brain natriuretic peptide (r= 0.41 p=0.0001), left ventricular ejection fraction (r=0.34, p=0.0009), aortic valve area index (r=0.33, p=0.0017), and global longitudinal strain (r=0.52, p<0.001). Patients who experienced prior heart failure hospitalization had a significantly larger extent of myocardial fibrosis (3.3% vs. 7.0%, p=0.0002). Conclusions Extensive myocardial fibrosis was associated with various heart failure parameters in patients undergoing TAVI. Patients with a large extent of myocardial fibrosis may require early intervention and/or intensive heart failure medical therapy to prevent fibrosis progression.

Prognostic implications of guideline-directed medical therapy in functional mitral regurgitation: a meta-analysis

Abstract Background Randomized evidence of the role of heart failure medical therapy for patients with functional mitral regurgitation (FMR) is lacking. Purpose The present meta-analysis sought to investigate the independent long-term prognostic impact of the different medical categories recommended in heart failure, for subjects with FMR. Methods A systematic literature review was conducted in electronic databases to identify studies reporting the association of renin angiotensin system inhibitors (RASi), beta-blockers (BBs), and mineralocorticoid receptor antagonists (MRAs) with outcomes in FMR. A random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome in each medical category. Results The final sample comprised 12 studies with 6,715 FMR patients (Picture 1). The use of RASi and BBs was associated with a significantly lower risk for all-cause mortality (HR 0.52 [0.39-0.68]; p <0.00001, I2 =62 % and HR 0.62 [0.49-0.77]; p <0.0001, I2 =44 % respectively) and for the composite outcome (HR 0.54 [0.44-0.67]; p <0.00001, I2 =33 % and HR 0.62 [0.52-0.75], p <0.00001, I2 =35% respectively) in unadjusted models (Picture 2). Both RASi (aHR 0.73 [0.56-0.95], p =0.02, I2 =52%) and BBs (aHR 0.60 [0.41-0.88], p = 0.009, I2 =55%) retained their association with the composite outcome in pooled adjusted models (Picture 2). The prognostic benefit of using RASi or BBs was retained in subgroup analysis including only patients with moderate of severe FMR. MRAs did not demonstrate a significant association with improved outcomes in FMR. Conclusions RASi and BBs appear to have a favorable prognostic impact in patients with FMR, regardless of regurgitation severity.Study flow chart for study selectionPharmacotherapy and prognosis in FMR

Impact of discharge checklist on guidelinedirected medical therapy and mid-term prognosis in heart failure.

Despite the proven benefit of the guideline-directed medical therapy (GDMT), it remains underutilized in patients hospitalized with acute heart failure (HF). We aimed to evaluate the impact of the discharge checklist on GDMT installation and the prognosis of HF patients. This study was a single-center, observational study that included all patients admitted for HF from March 2021 to February 2023. The data were retrieved from electronic medical records and discharge checklists. A comparison was conducted between the checklist group and the non-checklist group. The primary endpoint was a composite of all-cause mortality or readmission for HF within 6 months. The checklist was completed for 537 patients (checklist group) and not for 187 patients (non-checklist group). The proportion of patients to whom two or more components of GDMT were prescribed was significantly higher in the checklist group than in the non-checklist group (59.6% vs 42.2%, p < 0.001). The checklist group exhibited a significantly lower primary outcome compared to the non-checklist group (27.4% vs. 36.4%, HR 0.73, 95% CI 0.55-0.98, p = 0.036). The effect of the checklist was more prominent in HF with reduced ejection fraction (HR 0.51, 95% CI 0.34-0.77, p = 0.001) than in HF with mildly-reduced and preserved ejection fraction (HR 0.91, 95% CI 0.58-1.42, p = 0.676) (p for interaction = 0.06). The implementation of the discharge checklist was associated with an improvement in GDMT prescription and an improved prognosis in patients with HF with reduced ejection fraction.

Impact of Psoas Muscle Area Index on Short- and Mid-Term Mortality in Patients Undergoing Valve Surgery for Infective Endocarditis: A Retrospective Analysis.

Background: Sarcopenia, characterized by the loss of skeletal muscle mass, is an emerging comorbidity associated with poor outcomes in cardiovascular surgery. Its impact on mortality in patients undergoing valve surgery for infective endocarditis (IE) remains underexplored. This study investigates the relationship between sarcopenia, measured by the Psoas muscle area index (PMAi), and mortality in patients with IE undergoing valve surgery. Materials and Methods: We retrospectively analyzed 68 patients with IE who underwent valve surgery at a tertiary care center from 2013 to 2021. Sarcopenia was defined as being in the lowest quartile of PMAi, measured via preoperative computed tomography (CT). Baseline characteristics, survival outcomes, and factors influencing mortality were analyzed using Kaplan-Meier survival curves and Cox proportional hazards regression. The predictive value of PMAi for 1-year and 3-year mortality was assessed via receiver operating characteristic (ROC) curves. Results: Sarcopenia was strongly associated with increased mortality at both 1-year (HR: 0.378, p = 0.010) and 3-year follow-ups (HR: 0.457, p = 0.012). Female sex (OR: 275.748, p < 0.001) and older age (OR: 9.995, p = 0.003) were significant predictors of sarcopenia. Chronic kidney insufficiency (CKI) and the use of heart failure medication therapy also significantly impacted survival outcomes. Conclusions: Sarcopenia is a strong independent predictor of short- and mid-term mortality in patients undergoing valve surgery for IE. Routine radiological assessment of sarcopenia using PMAi could improve risk stratification and guide preoperative interventions. Tailored management strategies, especially in older women and patients with CKI, may enhance outcomes in this high-risk population.

Implementation and evaluation of specialist heart failure pharmacist prescribing clinics.

Medications form the basis of treatment for heart failure (HF) and adherence is crucial as untreated HF has a mortality of greater than 30%. As such, specialist HF pharmacists with expertise in prescribing and promoting adherence have become an integral part of the wider HF multidisciplinary team (MDT). To implement specialist HF pharmacist prescribing clinics and evaluate their impact. An integrated HF team at a tertiary London hospital. The clinic was initially developed to facilitate the introduction of sacubitril-valsartan evolving to 6 dedicated clinics/week. A dedicated electronic referral pathway was created to channel referrals to the specialist clinic, and referral criteria expanded to all patients requiring optimisation of medical therapy. Data were retrospectively collected for patients with heart failure with reduced ejection fraction seen in the HF pharmacist clinic between September 2021 and July 2022. Overall, 114 patients were seen (mean age 66years, 78 male). The mean time to medication optimisation was 3months (averaging 1 appointment/month). The number on optimised doses of guideline-directed medical therapy, increased significantly from 8% at first appointment to 76% on discharge (p < 0.001). The HF pharmacists reviewed all medications and optimised non-HF medications for 17.5% (n = 20) of patients. HF pharmacists can optimise patients' HF and non-HF medical therapy typically within 3months. By reviewing all prescribed medications, HF pharmacists provide a holistic review of all medications. They can play a vital role in addressing the underutilisation of HF medical therapy and thereby improving patient outcomes.

Efficacy, Safety and Mechanistic Impact of a Heart Failure Guideline-Directed Medical Therapy Clinic

BackgroundAlthough clinical evidence supports rapid institution of guideline-directed medical therapy (GDMT) for heart failure (HF), in actual practice, there remain large gaps in adherence to guideline recommendations. Recent data support safety and efficacy of rapid GDMT implementation; however, rapid GDMT deployment within a general cardiology environment remains unexplored. ObjectivesThe purpose of this study was to evaluate the efficacy and safety of a GDMT clinic within a general cardiology practice relative to usual care, the impact on prescription of GDMT, HF symptoms, N-terminal pro–B-type natriuretic peptide concentrations and echocardiographic parameters of remodeling. MethodsIndividuals with HF with an abnormal ejection fraction (<50%) referred to the GDMT clinic underwent rapid GDMT titration with close monitoring of clinical data. Rates of GDMT prescription were compared with a matched reference group. Patients underwent echocardiography at baseline and after GDMT clinic completion. ResultsA total of 114 persons were treated in GDMT clinic. The mean age was 67.6 ± 14.6 years, and 32 (28%) were women. Among those referred, 100 (87.7%) had no contraindications for 4-drug GDMT. From baseline to clinic completion (median 15.8 weeks [Q1-Q3: 10.7-23.0 weeks]), patients without medication contraindications experienced significant increases in 4-drug GDMT use (from 21% to 88%; P < 0.001); of 4-drug GDMT recipients, 92% received angiotensin receptor neprilysin inhibitor. GDMT clinic participants achieved higher medication doses than those in usual care, with greater achievement of ≥50% target dose of angiotensin receptor neprilysin inhibitor (52% vs 8%), beta-blocker (78% vs 6.2%), mineralocorticoid receptor antagonist (98% vs 15.6%), and sodium-glucose cotransporter 2 inhibitors (92% vs 6.2%). Target doses of all 4 drugs were reached in nearly 1 in 4 participants. HF symptoms improved (94% to 75% NYHA functional class II/III; P < 0.001) and N-terminal pro–B-type natriuretic peptide concentration decreased (median 587 to 534 ng/L; P = 0.03) despite loop diuretic reduction. Additionally, we observed an absolute 6% LVEF increase (from 37% [Q1-Q3: 31%-41%] to 43% [Q1-Q3: 38%-53%]; P < 0.001) and substantial decrease in moderate or severe mitral regurgitation. GDMT titration was well-tolerated. ConclusionsRapid GDMT implementation via an outpatient GDMT clinic was effective, safe, and associated with improvement in key clinical parameters. The more widespread role of GDMT clinics to improve HF care warrants further study.

Hospital Heart Failure Medical Therapy Score and Associated Clinical Outcomes and Costs.

A composite score for guideline-directed medical therapy (GDMT) for patients with heart failure (HF) is associated with increased survival. Whether hospital performance according to a GDMT score is associated with a broader array of clinical outcomes at lower costs is unknown. To evaluate hospital variability in GDMT score at discharge, 90-day risk-standardized clinical outcomes and costs, and associations between hospital GDMT score and clinical outcomes and costs. This was a retrospective cohort study conducted from January 2015 to September 2019. Included for analysis were patients hospitalized for HF with reduced ejection fraction (HFrEF) in the Get With the Guidelines-Heart Failure Registry, a national hospital-based quality improvement registry. Study data were analyzed from July 2022 to April 2023. GDMT score at discharge. Hospital variability in GDMT score, a weighted index from 0 to 1 of GDMT prescribed divided by the number of medications eligible, at discharge was evaluated using a generalized linear mixed model using the hospital as a random effect and quantified with the adjusted median odds ratio (AMOR). Parallel analyses centering on 90-day mortality, HF rehospitalization, mortality or HF rehospitalization, home time, and costs were performed. Costs were assessed from the perspective of the Centers of Medicare & Medicaid Services. Associations between hospital GDMT score and clinical outcomes and costs were evaluated using Spearman coefficients. Among 41 161 patients (median [IQR] age, 78 [71-85] years; 25 546 male [62.1%]) across 360 hospitals, there was significant hospital variability in GDMT score at discharge (AMOR, 1.23; 95% CI, 1.21-1.26), clinical outcomes (mortality AMOR, 1.17; 95% CI, 1.14-1.24; HF rehospitalization AMOR, 1.22; 95% CI, 1.18-1.27; mortality or HF rehospitalization AMOR, 1.21; 95% CI, 1.18-1.26; home time AMOR, 1.07; 95% CI, 1.06-1.10) and costs (AMOR, 1.23; 95% CI, 1.21-1.26). Higher hospital GDMT score was associated with lower hospital mortality (Spearman ρ, -0.22; 95% CI, -0.32 to -0.12; P < .001), lower mortality or HF rehospitalization (Spearman ρ, -0.17; 95% CI, -0.26 to -0.06; P = .002), more home time (Spearman ρ, 0.14; 95% CI, 0.03-0.24; P = .01), and lower cost (Spearman ρ, -0.11; 95% CI, -0.21 to 0; P = .047) but not with HF rehospitalization (Spearman ρ, -0.10; 95% CI, -0.20 to 0; P = .06). Results of this cohort study reveal that hospital variability in GDMT score, clinical outcomes, and costs was significant. Higher GDMT score at discharge was associated with lower mortality, lower mortality or hospitalization, more home time, and lower cost. Efforts to increase health care value should include GDMT optimization.

Health insurance and clinical outcomes in patients with chronic heart failure in Latin America: an observational study of the Colombian Heart Failure Registry (RECOLFACA).

The effect of the health insurance type on the prognosis of heart failure (HF) patients in Colombia and Latin America is poorly known. We aimed to analyze the characteristics of HF patients that participated in the Colombian Heart Failure Registry (RECOLFACA) as stated by their health insurance type and their relationship with the immediate prognosis of these patients. Patients with HF diagnosis were included in the RECOLFACA registry between 2017-2019. The registry was conducted in 60 centers in Colombia. All-cause mortality was the principal outcome. To evaluate the impact of health insurance on mortality, a Cox proportional hazards regression model was used. The Kaplan-Meier analysis was performed to compare survival probabilities according to insurance type. All statistical analyses were two-tailed and were considered significant with a p value < 0.05. Of the 2,528 participants enrolled in the registry, 99% held details about their health insurance. Of those, 897 patients (35.6%) were covered by public insurance. These patients were significantly younger, with a lower proportion of men, more frequently from rural origin, and lower prevalence of most comorbidities (omitting hypertension, chronic obstructive pulmonary disease (COPD), and Chagas disease) than those with private insurance. Furthermore, patients with public insurance had a worse functional class, as well as a poorer quality of life, and lower frequency of use of implantable devices, while exhibiting similar prescription rates of triple medical therapy for HF. Finally, no differences in short-term mortality were observed between the two groups (HR 1.09; 95% CI 0.79, 1.51). The type of health insurance represents a condition related with relevant differences in the profile of patients with HF in Colombia. Despite this, no significant differences were detected in the short-term prognosis of these patients based on the type of health insurance.

Insights on prevalence and incidence of anemia and rapid up-titration of oral heart failure treatment from the STRONG-HF study.

Anemia is one of the most frequent comorbidities in patients with heart failure (HF), which potentially can interfere with the effect of guideline-recommended HF medical therapy and can be associated with the use of neurohormonal blockers. The aim of this analysis was to determine the prevalence and changes of anemia status in the STRONG-HF study, its association with clinical endpoints, and possible interaction of the presence of anemia with the efficacy and safety of high-intensity HF treatment. The design and main results of the study have been previously described. Patients were randomized within 2days prior to anticipated hospital discharge after HF worsening in a 1:1 fashion to either high-intensity care (HIC) or usual care (UC). Baseline characteristics, clinical and safety outcomes, and treatment effect of HIC vs. UC on the primary and secondary outcomes were compared in groups based on baseline anemia. In addition, dynamics of hemoglobin during the study follow-up and predictors of incident anemia at 90days were investigated. The proportion of anemia in 1077 STRONG-HF patients at enrollment was 27.2%, while at 90days, it changed to 32.1%. The primary composite outcome occurred in 18.2% of patients without baseline anemia, and 22.5% of patients with baseline anemia (unadjusted HR 1.27; 95% CI 0.90-1.80), a difference that did not reach statistical significance. However, patients with baseline anemia had significantly less improvement of EQ-VAS questionnaire values from baseline to day 90 (adjusted LS-Mean difference -2.34 (-4.37, -0.31), P = 0.02). During the study, anemia developed in 19.4 and 14.6% in HIC and UC groups, respectively. The opposite phenomenon-recovery of anemia-occurred in 27.6 and 28.8% in HIC and UC groups (P = 0.1379). The predictors of incident anemia at 90days were male sex, geographical region other than Europe, ischemic etiology, higher glucose, and elevated uric acid at baseline. The percentages of optimal doses of renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were not different between anemic and non-anemic patients. High-intensity care strategy did not increase rate of incident anemia at 90days and reduced the rate of primary and secondary endpoints regardless of baseline hemoglobin. Hemoglobin level and status of anemia have a dynamic nature in the acute HF patients in the post-discharge period dependent on multiple factors. High-intensity HF treatment is safe and beneficial regardless of baseline hemoglobin level and presence of anemia. The improvement of quality of life is significantly lower in anemic HF patients implying specific attention to correction of this condition.

Cardiogenic shock in phaeochromocytoma multisystem crisis- a case report

Abstract Background Phaeochromocytoma multisystem crisis (PMC) is characterised by labile blood pressures (extremes of hypo- and/or hypertension) and multiorgan failure as a result of catecholamine excess. Initial stabilisation requires pharmacological and/or mechanical circulatory support, followed by institution of antihypertensives to correct the underlying pathophysiology. Case summary A previously well 40-year-old male developed sudden onset of breathlessness. On presentation, he was in shock with multiorgan failure. He required intubation, mechanical ventilation, dual inotropic support and renal replacement therapy. Bedside echocardiogram showed a severely impaired left ventricular ejection fraction (LVEF) of 25%. Coronary angiography revealed normal coronary arteries. In view of raised inflammatory markers and transaminitis, a CT abdomen/pelvis was performed. An incidental left adrenal mass was found. Further work-ups revealed raised plasma metanephrine and normetanephrine, 24-hour urine epinephrine and norepinephrine. A cardiac magnetic resonance (CMR) showed myocardial inflammation and reverse Takotsubo pattern of regional wall motion abnormality (RWMA). The diagnosis of cardiogenic shock and stress cardiomyopathy secondary to phaeochromocytoma multisystem crisis was made. He was subsequently initiated on α- and β-blockers and goal-directed medical therapy for heart failure. A 68Ga-DOTATATE scan showed avid tracer uptake of the left phaeochromocytoma. An interval CMR 3 weeks from presentation showed near normalisation of the LVEF and RWMA. He underwent a successful laparoscopic left adrenalectomy and was antihypertensive-free since. Conclusion The clinical suspicion for PMC as the cause of cardiogenic shock requires astute clinical judgement, while the management requires understanding of the underlying pathophysiology that call for multidisciplinary inputs.

Physician-Reported Reasons for Not Initiating Guideline-Directed Medical Therapy for Heart Failure

Physician-Reported Reasons for Not Initiating Guideline-Directed Medical Therapy for Heart Failure

Therapeutic Effects of Heart Failure Medical Therapies on Standardized Kidney Outcomes: Comprehensive Individual Participant-Level Analysis of 6 Randomized Clinical Trials.

Background: Kidney outcomes have been variably defined using non-standardized composite endpoints in key heart failure (HF) trials, thus introducing complexity in their interpretation and cross-trial comparability. We examined the effects of steroidal mineralocorticoid receptor antagonists (MRAs), the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan, and sodium-glucose cotransporter-2 (SGLT2) inhibitors on composite kidney endpoints using uniform definitions in 6 contemporary HF trials. Methods: Individual participant-level data from trials of steroidal MRAs (EMPHASIS-HF, TOPCAT Americas), ARNI (PARADIGM-HF, PARAGON-HF), and SGLT2 inhibitors (DAPA-HF, DELIVER) were included. The standardized composite kidney endpoint was defined as a sustained decline (a reduction in estimated glomerular filtration rate (eGFR) confirmed by a subsequent measurement at least 30 days later) in eGFR by 40%, 50%, or 57%, end-stage kidney disease, or renal death. eGFR was recalculated in a standardized manner using the 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Results: Among 28,690 participants across the 6 trials (median age 69 years [IQR, 62-76]; 9,656 [33.7% ] women), the proportion experiencing the composite kidney endpoint with a more stringent definition of a sustained decline in kidney function (eGFR threshold of 57%) ranged from 0.3% to 3.3%. The proportion of patients experiencing this endpoint with a less stringent definition (eGFR threshold of 40%) ranged from 1.0% and 10.0%. The steroidal MRAs doubled the risk of the composite kidney endpoint when applying the least stringent definition compared with placebo, but these effects were less apparent and no longer significant with application of more stringent definitions. ARNI appeared to consistently reduce the occurrence of the composite kidney endpoints irrespective of specific eGFR threshold applied. The potential benefits of SGLT2-inhibitors on the composite kidney endpoints appeared more apparent when defined by more stringent eGFR thresholds, although none of these effects individually were statistically significant. Conclusions: When applying standardized stringent kidney endpoint definitions, steroidal MRAs, ARNI, and SGLT2-inhibitors have either neutral or beneficial effects on kidney outcomes in HF. Applying less stringent definitions increased event rates but included acute declines in eGFR that might not ultimately reflect long-term effects on kidney disease progression.

Inpatient Use of Guideline-Directed Medical Therapy During HeartFailure Hospitalizations Among Community-Based Health Systems.

Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains underused. Acute heart failure (HF) hospitalization represents a critical opportunity for rapid initiation of evidence-based medications. However, data on GDMT use at discharge are mostly derived from national quality improvement registries. This study aimed to describe contemporary GDMT use patterns across HF hospitalizations at community-based health systems. The authors identified HF hospitalizations from 2016 to 2022 in a U.S. database aggregating deidentified electronic health record data from more than 30 health systems. In-hospital and discharge rates of GDMT use were reported for eligible HFrEF patients. Factors associated with inpatient GDMT use and predischarge discontinuation were evaluated with the use of multivariable models. A total of 20,387 HF hospitalizations among 13,729 HFrEF patients were identified. Renin-angiotensin system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists were administered during 70%, 86%, and 37% of eligible hospitalizations, respectively. Angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter 2 inhibitors were used in 17% and 8% of eligible hospitalizations, respectively. Discharge GDMT rates were low. Triple/quadruple therapy was administered in 26% of hospitalizations, falling to 14% on discharge. Predischarge GDMT discontinuations were associated with inpatient hypotension, hyperkalemia, and worsening renal function, but 43%-57% had no medical contraindications. In adjusted analyses, use of 3 or more GDMT classes was associated with fewer 90-day all-cause deaths and HF readmissions compared with less comprehensive GDMT. Inpatient GDMT use in a national analysis of HF hospitalizations was lower than reported in quality improvement registries. High discontinuation rates emphasize an unmet need for inpatient and postdischarge strategies to optimize GDMT use.

Qiliqiangxin Alleviates Imbalance of Inflammatory Cytokines in Patients with Dilated Cardiomyopathy: A Randomized Controlled Trial.

Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM. The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment. At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant. QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.