bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble guanylate cyclase in heart failure: A network meta-analysis and subgroup analyses of reduced and preserved ejection fraction
Authors: Abuelazm M , Attia A M , Albakri K , Jafar U , Almaadawy O , Elzeftawy M A , Mahmoud A , Ibrahim M , Abdelazeem B 
Published: November 2023

Abstract

Background
Heart failure (HF), either with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF), is a significant healthcare burden, with about one million hospitalizations annually in the United States alone. Soluble guanylate cyclase (sGC) stimulators have been investigated for HF treatment in several randomized controlled trials (RCTs). However, its place in the management guidelines of either HFrEF or HfpEF is still inconclusive.

Purpose
We aim to evaluate the efficacy and safety of sGC in HF and determine the most effective agent and dosage for the management of either HFrEF or HFpEF.

Methods
We conducted a systematic review and network meta-analysis synthesizing RCTs investigating sGC, including vericiguat, riociguat, and praliciguat for HF management, which were retrieved by systematically searching five databases until January 24th, 2023. Dichotomous outcomes were pooled using risk ratio (RR) along with confidence interval (CI). Frequentist random-effects network meta-analysis was conducted via R software using meta and netmeta packages.

Results
Eight RCTs with a total of 7307 patients were included in our analysis. Four RCTs investigated vericiguat, three investigated riociguat, and another investigated praliciguat. Five RCTs investigated HFpEF patients, and three investigated HFrEF patients. Vericiguat 10 mg significantly reduced the incidence of composite cardiovascular (CVS) mortality and HF hospitalization in HF (RR: 0.88, 95% CI [0.79; 0.98], P = 0.02) and in HFrEF (RR: 0.87, 95% CI [0.78; 0.97], P = 0.02); however, it was not effective in HFpEF (RR: 0.69, 95% CI [0.15; 3.05], P = 0.62). Also, vericiguat 10 mg showed no difference compared to placebo regarding the incidence of all-cause mortality (RR: 0.96, 95% CI [0.84; 1.10], P = 0.57), any adverse events (AEs) (RR: 0.94, 95% CI [0.83; 1.07], P = 0.34), any serious AEs (RR: 0.91, 95% CI [0.81; 1.01], P = 0.08), and any AEs leading to drug discontinuation (RR: 1.14, 95% CI [0.92; 1.40], P = 0.23). However, all other comparisons of vericiguat, riociguat, and praliciguat showed no difference compared to placebo regarding the composite CVS mortality and HF hospitalization, with a similar safety profile.

Conclusion
Only vericiguat 10 mg was effective in reducing the incidence of the composite CVS mortality and HF hospitalization in patients with HFrEF, with an acceptable safety profile. However, this observation is mainly weighted by the VICTORIA trial, constituting 69.2% of our analyzed sample size, which investigated vericiguat 10 mg in patients with HFrEF. Therefore, our data regarding other agents (riociguat and praliciguat) and HFpEF can be underpowered. This warrants further RCTs to clarify vericiguat 10 mg place in HFrEF management guidelines and to investigate sGC stimulators for HFpEF in large-scale adequately designed trials.Figure 1Figure 2
Initiation, titration, and discontinuation - utilization of heart failure medicines in England (EVOLUTION HF UK)
Authors: Zhang R , Mamza J B , Baruah R , Adamsson Eryd S , Bodegard J , Cleland J G F 
Published: November 2023

Abstract

Background
Guidelines advise early initiation and optimisation of several guideline-recommended pharmacological therapies (GRPTs) for managing heart failure (HF) with reduced ejection fraction. Recent guidelines have expanded this list to include two new classes of agents: sodium-glucose cotransporter 2 (SGLT2) inhibitors and angiotensin receptor neprilysin inhibitor (ARNI). Auditing real-world GRPT use is critical in closing the evidence-practice gap.

Purpose
To generate insights into utilization patterns of novel and established GRPTs after a recent hospitalization for HF (hHF) in England using administrative healthcare records.

Methods
New users of GRPTs within 12 months of a hHF discharge were identified using linked national electronic health records (Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics mortality data) between January 2021 — May 2022. Time to initiation of dapagliflozin (the only SGLT2 inhibitor approved for HF in January 2021), sacubitril/valsartan, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) were considered separately. Titration and discontinuation of the most frequently used drug for each pharmacological class was identified and analysed as representative of the entire class. Doses and discontinuation were assessed in the 12 months following initiation. If a new package isn't collected after the previous one ends, discontinuation is assumed until a new package is collected. Target dose was defined as ≥100% of the guideline-recommended dose.

Results
Overall, 16,090 new users of GRPTs were identified. Mean times from hHF to GRPT initiation were longer for novel agents (dapagliflozin or sacubitril/valsartan) than for established agents: 195 and 137 vs 48 to 73 days. Similarly, the cumulative percentage of patients initiating a GRPT within 100 days of hHF discharge were lower for novel agents (Figure 1). In the following 12 months, the average target dose achieved was higher for novel agents: 61.8% (dapagliflozin), 32.4% (sacubitril/valsartan), 8.5% (ACE inhibitor: ramipril), 5.9% (ARB: candesartan), 7.6% (beta-blocker: bisoprolol), and 6.6% (MRA: spironolactone). Corresponding discontinuation rates were 32.0%, 24.3%, 36.3%, 38.2%, 23.4%, and 50.1%, respectively (Figure 1 and 2).

Conclusion
In the UK, early initiation of novel GRPTs after recent hHF in routine clinical practice remains a challenge. For GRPTs requiring uptitration, few patients received the target dose in the 12 months after initiation, and many discontinued treatments. Conversely, dapagliflozin was associated with relatively higher rates of target dose achievement, perhaps because only a single fixed dose is recommended. Our data highlight the need for increased access to appropriate, timely and sustained HF therapeutic optimization.
The role of infliximab in treating refractory cardiac sarcoidosis
Authors: Ahmed R , Okafor J , Azzu A , Shi R , Wechalekar K , Baksi J , Collins P , Khattar R , Sharma R , Wells A , Kouranos V 
Published: November 2023

Abstract

Introduction
Cardiac sarcoidosis (CS) is associated with therapeutic challenges, and a high morbidity and mortality. Tumour necrosis factor alpha inhibitors like infliximab may be a treatment option for patients with persistent myocardial inflammatory activity despite conventional immunosuppressive treatment with steroids and steroid-sparing agents.

Purpose
To identify the safety and efficacy of infliximab in the treatment of refractory cardiac sarcoidosis.

Methods
We conducted a review of refractory CS patients who had been or were actively on treatment with Infliximab at our specialist tertiary care hospital from January 2017 to January 2023. Serial echocardiographic and FDG-PET scan changes as well as long term clinical data on morbidity and mortality was recorded.

Results
Six CS patients on infliximab were retrospectively identified. The mean age at CS diagnosis was 47.0±5.9 years and mean duration between CS diagnosis and starting infliximab was 21.4±14.2 months (Table 1). Infliximab was commenced due to persistent inflammation on FDG-PET scan and/or CMR despite being on at least two agents (prednisolone and methotrexate ± hydroxychloroquine) in 5 cases and prednisolone alone (intolerance to methotrexate) in one case. At baseline, 3 patients presented with ventricular arrhythmias, 2 with atrioventricular block and 2 with heart failure. After a mean follow up of 21.2±15.5 months of being on infliximab, 5/6 CS patients had decreased myocardial uptake on PET (1 was awaiting a scan) which included complete resolution of FDG-PET signal in one patient (Table 2). A trend in improvement of mean LVEF [52.7±6.6% to 60.2±5.9%, p = 0.10] and reduction of mean prednisolone dose [19.2±6.6mg to 11.3±7.0mg, p = 0.08] was observed during Infliximab treatment. None of the patients had worsening of LVEF or admission with acute heart failure whilst being on infliximab. A total of 4/6 patients had an Implantable Cardioverter Defibrillator device in situ at the time of Infliximab initiation. No major arrhythmias were observed during follow up. One patient died following complications of patent foramen ovale repair. There were three new cases of infection (1 pneumonia and 2 COVID-19 pneumonitis) and one case of renal cell carcinoma diagnosis three years after Infliximab treatment initiation. The drug safety was overall satisfactory since none of the patients required hospitalisation (Table 2). Case 2 patient stopped infliximab after 13 months of treatment and was found to have disease relapse seven months later. During a 20 month follow up of being on infliximab again, he demonstrated complete resolution of FDG uptake on subsequent FDG-PET scan.

Conclusion
This study supports the use of infliximab in refractory CS by demonstrating improvement in clinical, functional and tissue characterization parameters. However, infliximab is associated with an increased risk of infections.
Influence of background therapy on efficacy of dapagliflozin in patients with heart failure and improved ejection fraction
Authors: Pabon Porras M A , Clagget B L , Chatur S , Bhatt A S , Vaduganathan M , Fang J , Desai A , Jhund P , Martinez F , De Boer R , Kosiborod M , Lam C , Mcmurray J , Solomon S , Vaderny O 
Published: November 2023

Abstract

Introduction
Heart failure with improved ejection fraction (HFimpEF), defined as prior reduced left ventricular EF (LVEF) ≤40% with a subsequent measurement LVEF &gt;40%, is growing in prevalence, in part because of effective guideline directed medical therapy (GDMT) initiated when LVEF was ≤40%. These patients have been largely excluded from major HF clinical trials. The DELIVER trial demonstrated dapagliflozin to be beneficial in patients with symptomatic HFimpEF; whether this benefit differs by background medical therapy is unclear.

Purpose
We investigated the efficacy and safety of dapagliflozin in patients with HFimpEF by background HF GDMT (beta-blocker [BB], mineralocorticoid receptor antagonist [MRA], and ACEi/ARB/ARNI at baseline).

Methods
The DELIVER trial randomized patients with symptomatic heart failure and LVEF&gt;40% to dapagliflozin or placebo. Treatment effects on the primary endpoint, worsening heart failure or cardiovascular (CV) death, and its components were assessed by a GDMT composite score. We assigned 1 point each for baseline use of ACEi/ARB, evidence-based BB, or MRA, and 2 points for sacubitril/valsartan. The composite GDMT score could range from 0 (no GDMT) to 4 (triple therapy inclusive of sacubitril/valsartan).

Results
Among the 6,263 patients randomized, 1,151 (18%) had HFimpEF. Of those, 2% of patients were on no GDMT, 14% were on 1 GDMT, 47% were on 2 GDMT therapies, and 37% were on triple therapy at baseline (Figure 1). Patients treated with triple therapy, compared to those on less than 3 therapies, were younger, more likely male, have a history of myocardial infarction, less likely to have diabetes, had a lower baseline LVEF and systolic blood pressure, and higher eGFR. During 2.2 years of median follow-up, the incidence rate was 9.8 per 100 person-years among those on 1 or no medications at baseline compared with 8.6 per 100 person-years among those on 2 or 3 therapies. Relative benefits of dapagliflozin on the primary outcome were not significantly modified by baseline GDMT score (Pinteraction = 0.11), but absolute benefits appeared more pronounced in those receiving 1 or no medications at baseline (Figure 2). Serious adverse events were well-balanced between treatment arms in the HFimpEF cohort, including among those already treated with triple therapy.

Conclusions
In patients with HFimpEF, the benefits of dapagliflozin are similar irrespective of background GDMT. Dapagliflozin was safe and did not lead to higher risk of adverse events among those with HFimpEF, including those already treated with triple therapy.Figure 1Figure 2
Efficacy of sodium-glucose cotransporter 2 inhibitors on cardiorenal outcomes in older patients: a systematic review and meta-analysis
Authors: Yamashita I , Fujisaki T , Romeo F J , Fujisue K , Sueta D , Usuku H , Yamamoto E , Tsujita K 
Published: November 2023

Abstract

Background
Recent randomized controlled trials (RCTs) showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with increased risks of cardiovascular diseases. However, only limited data from subgroup analyses are available for older patients.

Methods
A systematic review was performed by searching PubMed, Cochran Central, and Embase through February 2023 for RCTs of SGLT2 inhibitors that were performed in adults and large (≥500 participants per group). Hazard ratios (HRs) and relative risk estimates in older subgroups ≥ 65 years were extracted from each study and were pooled using a random-effects meta-analysis. The primary outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The secondary outcomes were heart failure exacerbation, adverse renal outcomes, and a composite outcome of cardiovascular death or heart failure exacerbation.

Results
This study included 10 RCTs. SGLT2 inhibitors decreased the primary outcome but it did not reach statistical significance in older subgroups (HR, 0.86; 95% CI, 0.73-0.1.00, p = 0.06). Whereas SGLT2 inhibitors were associated with decreased risks of heart failure exacerbation (HR, 0.76; 95% CI, 0.67-0.87), adverse renal outcome (HR, 0.58; 95% CI, 0.43-0.77), and a composite outcome of cardiovascular death or heart failure exacerbation (HR, 0.76; 95% CI, 0.70-0.83).

Conclusions
SGLT2 inhibitors were associated with improved cardiovascular outcomes in older patients. Further therapeutic data and sufficient long-term safety data are warranted in this population.
Effect of dapagliflozin in patients with heart failure with mildly reduced or preserved ejection fraction treated with beta-blockers: the DELIVER trial
Authors: Peikert A , Bart B A , Vardeny O , Vaduganathan M , Claggett B L , Desai A S , Jhund P S , Kosiborod M N , Lam C S P , Martinez F A , De Boer R A , Hernandez A F , Shah S J , Mc Murray J J V , Solomon S D 
Published: November 2023

Abstract

Background
While beta-blockers are not recommended for the treatment of HFpEF according to the latest ESC and AHA/ACC/HFSA guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers might adversely influence clinical outcomes by limiting chronotropic response in HFpEF.

Purpose
To examine the contemporary use and implications of beta-blocker use in patients with HFmrEF or HFpEF.

Methods
In the DELIVER trial, a total of 6,263 patients with symptomatic HF with LVEF &gt;40% were randomized to dapagliflozin or placebo across 20 countries. Efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF.

Results
Overall, beta-blockers were used in 5,177 patients (83%), with wide variation ranging from Mexico (60%) to Poland (93%). Nearly all patients taking beta-blockers had at least 1 potential indication (n = 5,106 [99%]), such as hypertension (n = 4,623 [89%]), atrial fibrillation/flutter (n= 2,969 [57%]), coronary artery disease (n= 2,744 [53%]), or previous LVEF&lt; = 40% that has since improved (n = 991 [19%]). Beta-blocker use was not associated with a higher risk of the primary outcome in covariate-adjusted models (HR 0.68 [95% CI 0.59-0.80]; Left Panel). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR 0.82 [95% CI 0.72- 0.94]) and those not taking beta-blockers (HR 0.79 [95% CI 0.61-1.03]; P for interaction = 0.85), with similar findings for key secondary endpoints (Right Panel). Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use.

Conclusions
In patients with HFmrEF or HFpEF enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker, with virtually all these patients having at least 1 potential indication for use. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use.
Clinician perceptions and reasons for non-use of guideline-directed medical therapy for heart failure with reduced ejection fraction in the United States
Authors: Gulea C , Coyle C R , Bash L D , Tebbs K W , Hancock L N , Greene S J 
Published: November 2023

Abstract

Background
Despite evidence that guideline-directed medical therapy (GDMT) improves outcomes in heart failure with reduced ejection fraction (HFrEF), many eligible patients remain untreated in the United States (US).

Purpose
To explore reasons why patients are not receiving GDMT and physician perceptions in management of their patients.

Methods
We conducted a cross-sectional survey of HF treatment practices (Adelphi Real World Heart Failure Disease Specific Programme) between August 2022 and February 2023, following publication of the 2022 US HF guidelines recommended that patients with HFrEF receive: angiotensin receptor/neprilysin inhibitors (ARNI), beta-blocker, mineralocorticoid receptor antagonists (MRA), and SGLT-2 inhibitors (SGLT2i). A total of 63 cardiologists and 39 primary care physicians in the US provided clinical and treatment patterns data on adult patients with HFrEF (ejection fraction ≤ 40%) and completed an attitudinal survey detailing reasons for treatment initiation.

Results
The study group included 323 patients with HFrEF (median age of 67 years [IQR 56-74]; 39% females) of which 59.4% were White, 19.8% African American and 9.6% Hispanic; half of the sample was insured by Medicare (50.2%), followed by commercial insurance (36.5%). GDMT prescription rates are presented in Table 1. Overall, 57.3% were not prescribed ARNI (185/323), 16.4% (53/323) were not prescribed a beta-blocker; 71.5% (231/323) were not prescribed MRA, and 65.3% (211/323) were not prescribed SGLT2i. Among patients not receiving GDMT, the most frequently reported physician reason for not prescribing ARNIs (54.1%), beta-blockers (43.4%), MRAs (54.5%) or SGLT-2is (53.6%) was physician deemed the patient to be clinically stable (Table 2).
Most physicians (93.5%) reported being satisfied with treatment for patients with HFrEF and most (80.3%) believed that their patients with HFrEF were fully compliant with their treatments. Most physicians (91.2%) stated that they based their treatment decisions on both clinical experience and laboratory tests, as opposed to laboratory tests/imaging only (9.8%) or personal judgement only (16.7%).

Conclusions
In this cohort of patients with HFrEF from the US, the most common primary reason physicians reported for their patients not receiving GDMT was that the patient was clinically stable. Patient medication costs, contraindications, and proven intolerance were each reported as primary reasons for non-treatment in only a small minority of cases. These data suggest a strong culture of clinical inertia and lack of therapeutic urgency as the dominant driver of large gaps in use of GDMT in the US.GDMT prescriptions in HFrEF (n = 323)Physician-reasons for no GDMT
Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium
Authors: Blodgett Joanna M , Ahmadi Matthew N , Atkin Andrew J , Chastin Sebastien , Chan Hsiu-Wen , Suorsa Kristin , Bakker Esmee A , Hettiarcachchi Pasan , Johansson Peter J , Sherar Lauren B , Rangul Vegar , Pulsford Richard M , Mishra Gita , Eijsvogels Thijs M H , Stenholm Sari , Hughes Alun D , Teixeira-Pinto Armando M , Ekelund Ulf , Lee I-Min , Holtermann Andreas , Koster Annemarie , Stamatakis Emmanuel , Hamer Mark ,   ProPASS Collaboration, Gupta Nidhi , Stehouwer Coen , Savelberg Hans , de Galan Bastiaan , van de Kallen Carla , Thijssen Dick H J 
Published: November 2023

Abstract

Background and Aims
Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers.

Methods
Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours.

Results
The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7 h sleeping, 10.4 h sedentary, 3.1 h standing, 1.5 h LIPA, and 1.3 h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30 min of SB, sleep, standing, or LIPA with MVPA was associated with −0.63 (95% confidence interval −0.48, −0.79), −0.43 (−0.25, −0.59), −0.40 (−0.25, −0.56), and −0.15 (0.05, −0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day.

Conclusions
Compositional data analyses revealed a distinct hierarchy of behaviours. Moderate-vigorous physical activity demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing, or LIPA required substantial changes in daily activity.