bluuebunny/crossref_metadata_2025_split huggingface dataset:
The predicting system of prognosis for transthyretin amyloid cardiomyopathy
Authors: Nakashima N.N , Takashio S.T , Morioka M.M , Nishi M.N , Hirakawa K.H , Hanatani S.H , Tsujita K.T 
Published: October 2021

Abstract

Background
The staging systems for transthyretin amyloid cardiomyopathy (ATTR-CM) by high sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) are established. However, this system is not validated in Japan.

Purpose
The aim of study was to validate and modify the predicting system by BNP, hs-cTnT and eGFR of prognosis for Japanese patients with ATTRwt-CM.

Method
We evaluated in 158 consecutive patients with wild-type ATTR-CM. Univariate analysis revealed that increased hs-cTnT and B-type natriuretic peptide (BNP) levels and impaired renal function at diagnosis were associated with poor prognosis. We defined best cutoff value as follows by ROC curve analysis; hs-cTnT &gt;0.0565 ng/mL, BNP &gt;285 pg/mL and eGFR &lt;45 mL/min. We scored the index by adding 1 point for each factor and divide into low score group (0–1 point) and high score group (2–3 points).

Result
As shown figure, high score was associated with increased all-cause mortality and heart failure rehospitalization (log rank; P&lt;0.001, respectively).

Conclusion
This simple scoring system by hs-cTnT, BNP and eGFR, was useful for predicting prognosis in patients with wild-type ATTR-CM.

Funding Acknowledgement
Type of funding sources: None.
Optimal effectiveness of heart failure management: an umbrella review examining the effectiveness of interventions to reduce (re)hospitalizations in heart failure
Authors: Hafkamp F.J , Tio R , Otterspoor L , De Greef T , Van Steenbergen G , Van Veghel D ,   Nederlands Hart Netwerk
Published: October 2021

Abstract

Introduction
Heart Failure (HF) is a major health concern. It is the diagnosis with the highest readmission rates among all diseases. Nevertheless, it is estimated that up to 40% of hospitalizations are preventable. Yet, there remains a knowledge gape concerning which interventions contribute to effective prevention of HF hospitalization or readmission.

Purpose
This umbrella review, therefore, aims to systematically review all published meta-analysis conducted in the past 10 years that examined the effectiveness of interventions in reducing HF-related (re)hospitalization in heart failure patients.

Methods
An electronic literature search was performed in PubMed, Web of Science, PsycInfo, Cochrane Reviews, CINAHL and Medline to identify eligible studies published in English language from January 2010 up to the end of June 2020. To synthesize the data, a best-evidence synthesis was used in which meta-analyses were classified based on level of validity.

Results
A total of 54 meta-analyses were included which encompassed 262 unique RCTs (Figure 1). Strong evidence suggested that cardiac rehabilitation was inversely related to heart failure hospitalization. Furthermore, moderate evidence was found for the effectiveness of telemonitoring, loop diuretics and RAAS inhibitors in reducing HF-related hospitalizations. Furthermore, limited evidence suggested that multidisciplinary clinic or self-management promotion programs, catheter ablation, mitral valve therapy, CRT, SLGT-II inhibitors, statins, or ultrafiltration were negatively related to HF-hospitalization. Additionally, there remains conflicting evidence regarding the effect of cell therapy on HF-hospitalization. No evidence was found that anticoagulation or class II antiarrhythmics could reduce HF-related hospitalizations.

Conclusion(s)
This umbrella review is the first known review to highlight different levels of evidence regarding the effectiveness of several interventions in reducing HF-related hospitalization. It could guide future guideline development in optimizing care pathways for heart failure patients.

Funding Acknowledgement
Type of funding sources: None.
Tends in beta-blocker administration and in prevalence of indications for their usage in heart failure with preserved ejection fraction: an analysis of randomized clinical trials
Authors: Kokhan E , Kiyakbaev G , Kobalava Z.H 
Published: October 2021

Abstract

Background
Despite the lack of data supporting their benefits, beta-blockers (BBs) frequently prescribed for heart failure with preserved ejection fraction (HFpEF). This may be due to the other indications (coronary heart disease, atrial fibrillation, etc.) on the one hand and due to clinical inertia with translation evidence from heart failure with reduced ejection fraction to HFpEF on the other.

Purpose
To assess the trends in BBs administration and prevalence of the possible indications for their usage (hypertension, atrial fibrillation, coronary heart disease, myocardial infarction) in the participants of the randomized clinical trials (RCTs) of HFpEF.

Methods
A systematic literature search of PubMed database was performed. RCTs of pharmacological treatment of HFpEF carried out between 1993 and 2019 were used. Studies of the effectiveness of BBs usage, or studies performed in specific populations (HFpEF+coronary heart disease or HFpEF+hypertension, etc.) were excluded. Features at enrolment date and data on the frequency of BBs admission and the prevalence of hypertension, atrial fibrillation, coronary heart disease, and myocardial infarction were extracted. The trends over time of enrolment were analyzed using the Mann-Kendall test.

Results
Of the 718 filtered publications, 14 RCTs met the inclusion and exclusion criteria fully. In the most recent trials, up to 75–80% of patients received BBs. Time trends analysis revealed that between 1993–2019 years the frequency of BBs use among the participants of the RCTs of HFpEF significantly increased (tau=0.51, p=0.014). No such change was observed in the prevalence of coronary heart disease, myocardial infarction, hypertension, and atrial fibrillation (all p&gt;0.05). Prevalence of hypertension and atrial fibrillation showed a tendency toward increasing (tau=0.4, p=0.055 and tau=0.043, p=0.063, respectively) which became statistically significant for atrial fibrilation with the exclusion of the ALDO-DHF study (tau=0.5; p=0.042). The prevalence of myocardial infarction tended to decrease over time (tau=−0.73; p=0.06).

Conclusion
Over the last 20 years, the proportion of patients who used BB at enrolment in RCTs of HFpEF increased significantly. There was no statistically significant increase in the prevalence of the formal indications for their usage such as atrial fibrillation, hypertension, coronary heart disease or myocardial infarction. This fact requires attention since some retrospective studies have revealed that BBs use in HFpEF patients is associated with an increased risk of hospitalizations.

Funding Acknowledgement
Type of funding sources: None.
Novel antisense therapy targeting microRNA-132 in patients with heart failure
Authors: Taubel J , Hauke W , Rump S , Viereck J , Batkai S , Poetzsch J , Rode L , Weigt H , Genschel C , Lorch U , Theek C , Levin A.A , Bauersachs J , Solomon S.D , Thum T 
Published: October 2021

Abstract

Background
Cardiac microRNA-132-3p (miR-132) levels are increased in patients with heart failure (HF) and mechanistically drive cardiac remodelling processes. CDR132L, a specific antisense oligonucleotide, is a first-in-class miR-132 inhibitor that attenuates and even reverses HF in preclinical models.

Purpose
The aim of the current clinical Phase 1b study was to assess safety, pharmacokinetics, target engagement, and exploratory pharmacodynamic effects of CDR132L in patients on standard-of-care therapy for chronic ischaemic HF in a randomized, placebo-controlled, double-blind, dose-escalation study.

Methods
Patients had left ventricular ejection fraction between ≥30% and &lt;50% or amino terminal fragment of pro-brain natriuretic peptide (NT-proBNP) &gt;125 ng/L at screening. Twenty-eight patients were randomized to receive CDR132L (0.32, 1, 3, and 10 mg/kg body weight) or placebo (0.9% saline) in two intravenous infusions, 4 weeks apart in four cohorts of seven (five verum and two placebo) patients each.

Results
CDR132L was safe and well tolerated, without apparent dose-limiting toxicity. A pharmacokinetic/pharmacodynamic dose modelling approach suggested an effective dose level at ≥1 mg/kg CDR132L. CDR132L treatment resulted in a dose-dependent, sustained miR-132 reduction in plasma. Patients given CDR132L ≥1 mg/kg displayed median 23.3% NT-proBNP reduction, vs. 0.9% median increase in the control group. CDR132L treatment induced significant QRS narrowing and positive trends for cardiac fibrosis biomarkers.

Conclusions
This study is the first clinical trial of an antisense drug in HF patients. CDR132L was safe and well tolerated, confirmed linear plasma pharmacokinetics with no signs of accumulation, and suggests cardiac functional improvements. The indicative efficacy of this drug is very encouraging justifying additional clinical studies to confirm the beneficial CDR132L pharmacodynamic effects for the treatment of HF.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Cardior Pharmaceuticals GmbH
Lack of pro-arrhythmic potential for the novel soluble guanylate cyclase stimulator vericiguat: results from preclinical studies
Authors: Himmel H , Lagrutta A , Voemel M , Rupesh A.P , Imredy J.P , Johnson T , Vinzing M 
Published: October 2021

Abstract

Introduction
Vericiguat is an orally-administered soluble guanylate cyclase stimulator, developed for the treatment of symptomatic chronic heart failure (HF) in adult patients who have had a previous decompensation event. At the maximum therapeutic dose of 10 mg once daily in patients with HF, the protein-unbound plasma concentrations of vericiguat and its major pharmacologically inactive N-glucuronide metabolite M-1 are approximately 18 nmol/l and 43 nmol/l, respectively. As part of an integrated risk assessment, vericiguat and its M-1 metabolite were characterised electrophysiologically in vivo and in vitro. This was performed according to the International Council for Harmonisation standard S7B guideline and to recent related “best practice” revisions (draft ICH E14/S7B Q&A), being adopted as a result of the Comprehensive In Vitro Proarrhythmia Assay (CIPA) initiative.

Purpose
To assess the potential for a proarrhythmic risk from vericiguat and its M-1 metabolite in a series of preclinical studies.

Methods
The potential for proarrhythmic risk was investigated in conscious telemetered dogs and in a series of in vitro electrophysiological studies, including mechanistic ion channel studies, using both generally accepted and CIPA voltage-clamp protocols under conditions simulating normal and diseased physiological states. The ion channels studied were hERG, hNav1.5, hCav1.2, hKvLQT1/minK and hKv4.3. Transfected human embryonic kidney cell lines were used for the hERG, hNav1.5 and hKvLQT1/minK studies; transfected Chinese hamster ovary cell lines were used for the hCav1.2 and hKv4.3 studies.

Results
In dogs, administration of vericiguat as single oral doses was associated with dose-dependent decreases in arterial blood pressure (consistent with its mode of action) and compensatory increases in heart rate (Table 1). Heart rate-corrected QT (QTc) intervals were not prolonged by vericiguat to a clinically meaningful extent. Neither vericiguat nor its M-1 metabolite inhibited cardiac ion channels (hERG, hNav1.5, hCav1.2, hKvLQT1/minK and hKv4.3) at exposure multiples of &gt;150-fold (Table 2).

Conclusion
There was no preclinical evidence of proarrhythmic risk from the in vitro (simulating normal and diseased physiological states) and in vivo assessment of vericiguat or its major N-glucuronide metabolite M-1. This integrated risk assessment of non-clinical data supports the conclusion that administration of vericiguat 10 mg once daily in humans is not associated with meaningful QTc prolongation.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Funding for this research was provided by Bayer AG, Berlin, Germany and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Moderate intensity exercise training in heart failure with preserved ejection fraction: functional and structural benefits (The MIET-HFpEF trial)
Authors: El Amrawy A , Hassanein M , Ayad S , Eldabe F 
Published: October 2021

Abstract

Background
Heart failure with preserved ejection fraction (HFpEF) represents more than one half of the heart failure cases worldwide with increased morbidity and mortality. No proven medical treatment till now have shown mortality benefit in HFpEF. This study aims to elucidate the benefits of cardiac rehabilitation (CR) in HFpEF.

Methods
Sixty patients with HFpEF were included in 2 groups with 1:1 randomization.Group1 received usual medical care plus 2–3 rehabilitation sessions per week using moderate exercise with 40–75% of heart rate reserve on treadmill (up to 60 minutes according to the functional capacity). Group 2 received only usual medical care. Comparison between the 2 groups recording the percentage of improvement in echocardiographic diastolic function parameters, Minnesota living with heart failure questionnaire (MLWHFQ) and 6 -minute walk test at baseline and after 12 weeks.

Results
Group 1 showed significant improvement in the following: a. MLWHFQ (total score mean percentage of reduction) 305.60±158.44 versus (vs) 69.44±17.71 (p&lt;0.001).b. E/e' mean percentage of reduction 65.96±34.55 vs 18.23±13.98 (p&lt;0.001). c. Left atrial (LA) volume index mean percentage of reduction 27.86±13.27 vs 8.03±4.40 (p&lt;0.001). d. Pulmonary artery systolic pressure mean percentage of reduction was 33.85±14.68 vs 22.97±16.54 (p=0.02). e. 6–minute walk test 111.79±40.97 vs 46.33±11.58 (p&lt;0.001). f. Body mass index percentage of reduction 10.17±3.64 vs 2.80±1.60 (p&lt;0.001). g. Percentage of patients with down-grading of the degree of diastolic dysfunction: 10 patients (33.3%) vs 3 patients (10%) (P=0.028). h. However, there were no significant differences in left ventricular ejection fraction or other parameters as E/A ratio, LA dimension, isovolumetric relaxation time, degree of left ventricular hypertrophy.

Conclusion
CR not only added significant functional improvement in the quality of life and functional capacity in patients with HFpEF but also a significant structural improvement by improving the core items of diastolic function. In the light of the results of this study, we can recommend CR as a part of HFpEF management.

Funding Acknowledgement
Type of funding sources: None.
Impact of the Covid-19 pandemic on the device therapy for patients with the heart failure
Authors: Hall R , Chattopadhyay R , Pugh P.J 
Published: October 2021

Abstract

Introduction
Hospital admissions of patients with cardiovascular disease were markedly reduced in the UK in 2020 during the Covid-19 pandemic. In many institutions, including ours, patient care was redistributed from a specialty-based approach to a ward-based system, meaning some patients being admitted and managed under the care of non-specialist teams.

Purpose
We wished to examine the impact of these changes on heart failure (HF) patients presenting during the pandemic and on appropriate delivery of complex device therapies.

Methods
The study was undertaken in a large UK teaching hospital. The institution audit programme includes cardiac device therapy provision, aiming to ensure that implantable cardioverter defibrillators and cardiac resynchronisation therapy are offered to the target population in accordance with NICE guidance [Technology Appraisal 314]. In accordance with the guidance, patients admitted to hospital with serious ventricular arrhythmia, familial cardiac condition with high risk of sudden cardiac death (SCD), surgical repair of congenital heart disease (CHD) and patients with HF and LVEF&lt;36% were identified from hospital coding. Findings during the pandemic (March to August 2020) were compared with the same period in 2019. Fisher's exact test was used to compare proportions.

Results
Among non-HF patients, device therapy prescription was consistent in the two periods observed. Table 1 shows how many patients were eligible for device therapy and how many were offered it. Table 2 contains details of HF admissions, showing an 8% reduction in admissions during the pandemic. The proportion of patients eligible for device therapy did not change significantly. However, there was a significant reduction in the proportion of eligible patients who were offered device therapy (79% vs 94% p=0.03). In addition, during the pandemic there was a trend towards a greater chance of patients being considered too frail for device therapy (p=0.08). Among 12 patients overlooked for device therapy, 10 were not under the care of Cardiology. Among 31 patients considered too frail for device therapy, 26 were not under the care of Cardiology.

Conclusion
During the Covid-19 pandemic, a modest reduction in HF hospital admission was observed with a marked fall in identification of patients eligible for device therapy. Possible explanations include intense pressure to discharge patients quickly, an increased perception of patient frailty during a crisis and the lack of recognition of indications for device therapy when patients are under the care of non-specialists. These findings suggest that cardiac services should actively look for HF patients who may have missed out on life-saving device therapies during the pandemic.

Funding Acknowledgement
Type of funding sources: None.
Outcomes of COVID-19 infection in heart transplant recipients
Authors: Miklin D , Mantha A , Wolfson A , Vaidya A , Depasquale E 
Published: October 2021

Abstract

Background
Heart transplant recipients may be at increased risk for infection and adverse outcomes from infection with COVID-19. Management of these patients is complex, with limited data and no standard of care.

Purpose
We sought to describe the incidence and outcomes of COVID-19 infection in patients with a history of heart transplant.

Methods
Retrospective review of 235 heart transplant patients at a large academic medical center identified 31 patients with laboratory confirmed COVID-19 infection. Laboratory and clinical data were collected from our institution as well as other local hospitals patients had been treated at. Outcomes were followed from March 15, 2020 to March 15, 2021. All data was deidentified.

Results
In a cohort of 235 heart transplant patients, 31 patients were identified after testing positive for COVID-19 infection. The mean and median age of patients was 51.9 and 56.0 years respectively. 71% of patients were male and 29% of patients were female. The mean and median time from transplant to diagnosis was 6.54 and 6.50 years. Average ejection fraction prior to infection was 60.4%. Seventeen patients (55%) had atherosclerosis, ten patients (32%) had diabetes, fifteen patients (48%) had hypertension, and twelve patients (39%) had a history of smoking. 84% of patients were on three types of immunosuppression and 16% were on two. Eight patients (26%) were asymptomatic, six patients (19%) had acute hypoxic respiratory failure, and two patients (7%) had GI symptoms. Two patients had evidence of graft injury with mean AlloSure (donor derived cell free DNA) levels of 0.61%. Immunosuppressive regimens were decreased in 32% of patients and COVID-19 directed therapies were given in 32% of patients. The most common treatments were remdesevir (5 patients), steroids (3 patients), and bamlanivimab (2 patients). Thirteen patients (42%) were hospitalized and two patients (7%) died.

Conclusions
In a single center case series 31 patients were identified with COVID-19 infection. Nearly half of the patients required hospitalization, with one third of patients decreasing their immunosuppressive regimen and 7% mortality. Further investigation is needed to determine long term outcomes and optimal therapeutic regimen for COVID-19 in this unique population.

Funding Acknowledgement
Type of funding sources: None.
One year outcomes of heart failure multispecialty multidisciplinary team virtual meetings
Authors: Essa H , Oguguo E , Douglas H , Foster A , Walker L , Hadcroft J , Bellieu J , Kahn M , Rao A , Cuthbertson D , Akpan A , Wong C , Sankaranarayanan R 
Published: October 2021

Abstract

Heart Failure is frequently associated with several comorbidities such as ischaemic heard disease, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease and frailty. This level of complexity is best dealt with by a multispecialty multidisciplinary team (MDT) model.
This was a single centre observational study (January 2020-December 2020) that was undertaken in a British university hospital looking at effect of HF multispecialty virtual MDT meetings on HF outcomes. Patients acted as their own controls outcomes compared for equal period pre versus post MDT meeting. The multi-specialty meeting was conducted once monthly via video-conferencing. It consisted of heart failure cardiologists (from primary secondary and tertiary care), heart failure specialist nurses (hospital and community), nephrologist, endocrinologist, palliative care specialists, chest physician, pharmacist, pharmacologist and geriatrician. Recommendations were made as consensus from the multispecialty meeting. The main outcome measures were 1) number of hospitalisations and 2) outpatient clinic attendances 3) cost savings.
A total of 189 patients were discussed from January-December 2020. This was uninterrupted during the COVID-19 pandemic. The mean age was 70.3±18.1 years and median follow-up 6 months (range 1–13 months). The mean Charlson Co-morbidity score was 5.3±1.2 and Rockwood Frailty Score was 4.9±1. The mean number of outpatient clinic attendances avoided was 1.7±0.4. This reduced inconvenience to patients, saved patients money (transport and parking costs) and led to carbon footprint reduction. The MDT meeting total costs were £15,400 and the 31 clinic appointments they generated cost an estimated £3720. However, the MDT meetings prevented 277 clinic appointments (cost saving £33,352). Finally, the mean number of hospitalisations pre-MDT was 0.7 Vs 0.2 post MDT (p&lt;0.01) with a saving of around 730 bed days (estimated cost-saving £260,000).
The HF multispecialty virtual MDT approach provides seamless integration of primary care community services with secondary and tertiary care. Consensus decision from MDT meetings provides holistic approach for HF patients with comorbidities and frailty, and reduces inconvenience to patients by preventing the need to attend multiple specialty clinics. This approach can also lead to significant cost-savings to the healthcare system.

Funding Acknowledgement
Type of funding sources: None.