bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opportunities for clinician education in the pharmacotherapy of stable heart failure
Authors: Murray P , O'Connor C.T , Maher V , Moore D 
Published: October 2021

Abstract

Introduction
Heart failure (HF) is a commonly encountered clinical entity in the developed world, and is estimated to cost 660m euro annually to the Irish exchequer. Evidence supporting the benefit of multi disciplinary care in reduction of readmission rates has prompted the establishment of specialist HF clinics, resulting in improved medication adherence and early recognition and treatment of mild decompensation, thus averting the need for hospital admission. In contrast, the role of the hospital generalist and the general practitioner in the management of stable HF is under-emphasised despite evidence that optimal medical therapy reduces readmission and its attendant costs. The aim of this survey was to assess knowledge of pharmacotherapeutic options amongst generalists, and identify opportunities for education, in order to further optimise guideline-directed medical therapy while the patient awaits specialist input.

Methods
We distributed a 14 item questionnaire regarding indications for HF medications (as per ESC guidelines) to doctors in medicine and general practice throughout Ireland.

Results
There were 127 responses from 27 centres (117 analysed). Median years of practice was 4. Table 1 depicts the breakdown of clinicians who correctly identified HFrEF as an indication for each of the major drug classes. More than 20% of clinicians at all grades failed to identify HFrEF as an indication for beta blocker therapy. There was a higher level of knowledge amongst junior doctors in the prescription of mineralocorticoid receptor antagonists (p≤0.05) but no statistical difference in knowledge of other drug classes. Only 26% of participants who felt comfortable with initiation and up-titration of beta blockers (N=89) correctly identified an optimal target heart rate of less than 70 beats per minute. Twenty-four percent of respondents (N=28) were unaware of a specialist HF service that catered to their institution. Ninety-seven percent (N=113) felt that their practice would benefit from further education on HF pharmacotherapy.

Conclusion
The high prevalence of HF in Ireland and costs associated with admission for decompensation necessitates a sound knowledge of its management amongst generalists. Results of this survey suggest a need, and indeed a demand, for further education and support surrounding pharmacotherapy of stable heart failure.

Funding Acknowledgement
Type of funding sources: None.
Gender differences in reverse cardiac remodeling following initiation of sacubitril/valsartan in heart failure with reduced ejection fraction: real world experience
Authors: Savage P.S , Campbell P.C , Adams S.A 
Published: October 2021

Abstract

Background
Gender related differences in physiology and pharamocokinetics have long been appreciated; however, the clinical relevance of these differences are unclear (1). Sacubitril/Valsartan has become established as a guideline directed therapy for the treatment of heart failure with reduced ejection therapy (HFref) and NYHA class II-IV symptoms. Interestingly; recent secondary analysis of key trials such as PARAGON-HF and PARADIGM, have highlighted possible differential gender specific benefits from Sacubitril/Valsartan therapy (2).
We therefore sought to evaluate if there were gender specific effects of Sacubitril/Valsartan on both quantitative and qualitative measures of heart failure outcomes.

Methods
We performed a retrospective data interrogation of all patients commenced on Sacubitril/valsartan therapy in the SHSCT between 2016 and 2019. Data was extracted using electronic care records. Local ethical approval was granted.
The primary endpoint were change in LVEF% on echocardiography and improvement in QOL (defined as NYHA score) at one year following initiation of Sacubitril/Valsartan.
Differences in means between baseline and one year were assessed using a paired student's t-test. Interaction of gender on respective outcomes was assessed using a two way ANOVA. Significance defined as p&lt;0.05. Data expressed as mean ± SD. Analysis performed using SPSS™.

Results
A total of 422 patients were included (mean age 69.1±12.1 years; 66% male). The predominant NYHA class' were II (n=298, 67.7%) and III (n=118, 26.8%). Aetiology and comorbidities were similar across male and females. In both groups, there was a statistically significant improvement in LVEF% at one year following initiation of Sacubitril/Valsartan (female; 27.1±8.6 to 34.6±9.5, n=40 p&lt;0.01) (male; 27.4±7.5% to 32.6±9.3%, n=91, p&lt;0.01). There was a statistically significant interaction between gender and degree of reverse cardiac remodeling defined as LVEF% on echocardiography following initiation of Sacubitril/Valsartan (F[2,52]=8.280, p=0.04, partial n2=0.27) (Figure 1).
Similarly, there was a significant improvement in NYHA scores in both groups (male; 2.2±0.5 to 2.02±0.6, n=331, p&lt;0.05) (female; 2.29±0.6 to 2.07±0.5, n=91, p&lt;0.05) (Figure 2). However; there was no statistically significant interaction between gender and NYHA score following initiation of Sacubitril/Valsartan (F[2,52]=0.133, P=0.716, partial n2≤0.0).

Conclusion
Sacubitril/Valsartan produced significant improvement in reverse cardiac remodelling and QOL measures in both groups. Notably, had a stronger effect of reverse cardiac remodelling in women – suggesting possible gender specific differential benefits.

Funding Acknowledgement
Type of funding sources: None.
Normal values for indexed left atrial end-systolic volume by two- and three-dimensional echocardiography. A cross-sectional population study
Authors: Eriksen-Volnes T , Nes B , Wislof U , Lovstakken L , Dalen H 
Published: October 2021

Abstract

Background
The left atrium volume and function gives important prognostic and diagnostic information. Normal values for left atrial end-systolic volume index (LASVI) is derived from 4-chamber and 2-chamber views or three-dimensional (3D) imaging. In current recommendations LASVI above 34 ml/m2 has been regarded dilated when assessing diastolic function and left ventricular filling pressures. It is not known if improved image quality by new scanners or more dedicated atrial focused views provide the same normal reference ranges.

Material and methods
We examined a large sub-population participating in a population based health study by high-end echocardiographic scanners. LA volume was assessed at end-systole in two-dimensional (2D) recordings focusing on the left atrium to avoid foreshortening. Additionally, 3D full volume recordings were acquired stitching 2–4 cardiac cycles when feasible using breath hold. All echocardiograms were analyzed offline using dedicated commercial software with manual tracing of the endocardial border and calculation of volume by the summation of discs method in 2D recordings.

Results
2462 of 5763 invited persons was examined by echocardiography. 1048 persons were excluded due to known heart disease, atrial fibrillation, antihypertensive treatment, diabetes mellitus or findings of clear pathology on echocardiography leaving 1414 persons presumed free of cardiovascular disease or major risk factors for the analyses.
Mean ± SD age was 57.9±12.4, and 55.8% was females. Mean (SD) LASVI in females and males were 27.6±9.7 ml/m2 and 30.7±11.1 ml/m2 by 2D imaging, respectively. Similarly, mean ± SD LASVI in females and males were 29.1±6.8 ml/m2 and 30.5±7.9 ml/m2 by 3D. The distribution of LASVI by age is showed in figure 1. The mean ± SD difference between 2D and 3D intra-individual measurements were 0.31±9.0 ml/m2 corresponding to 1.1%. By 2D assessment 24.1% of this presumed healthy cohort had a LASVI over 34 ml/m2, with more males than females had enlarged left atria by this definition (32.7% vs 20.1%, p&lt;0.001).

Conclusion
New reference ranges for left atrial size is provided for 2D and 3D recordings. By dedicated 2D recordings normal values are larger than previously recorded, and the difference between 2D and 3D recordings are less than previously reported.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): NTNU and the HUNT study Figure 1. Indexed left atrial end-systolic volume, summation of discs method using adjusted left atrial view vs age. The red line denotes 34 ml/m2 used as the cut-off value in present guidelines.
Right ventricular dysfunction is a predictor of non-response to cardiac resynchronization therapy
Authors: Neves Pereira M , Leite P.V.H , Dias G , Cardoso A.F , Tinoco M , Azevedo O , Lourenco M , Ribeiro S , Ferreira F , Sanfins V , Lourenco A 
Published: October 2021

Abstract

Introduction
Cardiac resynchronization therapy (CRT) has been of great benefit to many heart failure (HF) patients with reduced ejection fraction (EF) and intraventricular conduction delay. However, approximately 30% of patients fail to respond to CRT. We investigated baseline characteristics that might influence response to CRT.

Methods
We retrospectively enrolled 227 patients undergoing CRT implantation between 2013 and 2020 according to the guidelines. 118 patients were included in our analysis, from whom all data were available. Clinical, electrocardiographic and echocardiographic parameters were evaluated at baseline and 6 months after CRT implantation. Response to CRT was defined as an increase in left ventricular ejection fraction (LVEF) &gt;10%. Right ventricular systolic dysfunction (RVSD) was defined as S' velocity &lt;9.5 cm/s or tricuspid anular plane systolic excursion (TAPSE) &lt;17 mm. Chronic kidney disease (CKD) was defined as GFR &lt;60 ml/min/1.73m2.

Results
118 patients were included (mean age 69±11 years, 66.1% males, 39.8% ischemic etiology; 35,6% atrial fibrillation, baseline LVEF 27,6±6%). After 6 months of CRT, 65 patients (55.1%) were considered responders. Responders were more frequently female than non responders (43,1% vs 22,6, p=0.02). Atrial fibrillation and CKD were more prevalent in non responders (47,2% vs 26,2%, p=0.018; 62,3% vs 21,5%, p&lt;0.001, respectively). RVSD was present in 60,4% of non responders vs 16,9% of responders (p&lt;0.001). In responder group, the mean S' velocity was 10,9±2,1 cm/s vs 9,1±2,1 cm/s in non responder group, p&lt;0.001. The mean TAPSE was also higher in responder group (20,3±7,2 mm vs 16,5±4,4 mm, p=0.031). On multivariate analysis only RVSD (OR 7,754; 95% CI 2,968 – 20,282 p&lt;0.001] and CKD (OR 5,434; 95% CI 2,109 – 14,002; p&lt;0.001) were independently associated with non-response to CRT.

Conclusion
From a range of preoperative characteristics, multivariate analysis only identified RVSD and CKD as independent predictors of CRT response, with S' &lt;9,5 cm/s and TAPSE &lt;17 mm associated with non-response to CRT. This study highlights the importance of routine RV assessment in order to improve patient selection and optimize CRT response in heat failure patients.

Funding Acknowledgement
Type of funding sources: None.
Impact of kidney disease on left ventricular assisted device outcomes: insight from National Readmission Database
Authors: Shatla I , Abumoawad A , Cheng A.-L , Lopez Candales A 
Published: October 2021

Abstract

Introduction
Improvements in device technology, appropriate patient selection and timing of left ventricular assist device (LVAD) implantation have allowed this technique as the preferred destination therapy for advanced end-stage heart failure (HF) patients whom are not candidates for heart transplantation. Unfortunately, up to a third of these patients still experience poor outcomes following LVAD implantation. Although some clinical factors have been identified as potential risk factors for these poor outcomes, there is paucity of data regarding the impact of baseline kidney disease following LVAD implantation.

Methods
We used the Nationwide Readmission Database (NRD), identifying patients who underwent implantable LVAD placement 2010–2017 using ICD-9 and 10 codes. Patients were stratified into 3 mutually exclusive groups based on presence and severity of chronic kidney disease (CKD) during the LVAD placement hospitalization: non-CKD, CKD and end stage renal disease requiring dialysis (CKD-D). Outcomes were all-cause and cause-specific 30-day readmissions as well as 90-day readmission.

Result
Within 30 days after discharge 28.5% of patients were readmitted. Of those without CKD, 27.8% were readmitted, compared to 29% of those with CKD and 31% of those with CKD-D. Compared to non-CKD (adjusted for demographics, index hospitalization and chronic comorbidity factors, and year), odds of 30-day readmission were 1.542 [95% CI 1.028–2.313] times higher for those with CKD-D, whereas those with CKD had similar 30-day readmission risk (OR 1.074 [95% CI 0.951–1.213]). Those with CKD and CKD-D had higher risk of 30-day readmission for acute (HF), bleeding and transfusion need.
Within 90 days after discharge 48.88% of patients were readmitted. Of those without CKD, 46.2% were readmitted, compared to 50%of those with CKD and 45% of those with CKD-D. Odds of 90-day readmission were 1.203 (95% CI 1.088–1.330) times higher for those with CKD than non-CKD group, Also those with CKD-D requiring dialysis had higher 90-day readmission risk (OR 1.287 [95% CI 0.954–1.736]) when compared to non-CKD. Those with CKD had higher risk of 90-day readmission for acute (HF), gastrointestinal bleeding and arrhythmia while those with CKD-D had higher risk of 90-day readmission for DVT and anemia. There was no difference in 30-day and 90-day readmission between all groups for stroke, device related thrombosis or infection.

Conclusion
It appears, based on our analysis, that although having CKD does not confer additional risk for either 30 or 90-days readmissions; these post LVAD patients have a greater risk of acute HF exacerbation, bleeding and arrhythmias. We believe that these results are very important and should be included into future risk models when deciding on LVAD implantation.

Funding Acknowledgement
Type of funding sources: None.
Intermittent therapy with levosimendan in patients with advanced heart failure
Authors: Blaschke M , Kiwi A , Hagl C , Weis M 
Published: October 2021

Abstract

Introduction
Therapeutic options for patients with advanced heart failure on the high-urgent (HU) heart transplant (HTx) waiting list are limited. In view of the limited data on the usefulness of classic inotropes, the calcium sensitizer levosimendan (Lev) may be a possible alternative for patients in need of a repetitive therapy with an inotropic agent as a bridge to HTx.

Method
In a single-center open-label study we retrospectively analyzed data from 34 HU-listed patients (from a total collective of 95 HU patients) who repetitively received Lev (12.5 mg; 0,05–0.1 μg/kg/min over 24–48h) in 2–8 weeks intervals due to cardiac instability and/or progressive second organ dysfunction. Potential side effects as well as changes of kidney, liver and heart functional parameters were evaluated (0–6 days before, 4–8 days and 14–20 days after Lev infusion).
Patient collective: age 51±10 years, 6 women, 28 men; NYHA stage III-IV.
11 Patients with ischemic cardiomyopathy (32%), 19 patients with dilated cardiomyopathy (56%), 4 patients with arrhythmogenic right ventricular cardiomyopathy (12%).

Results
The waiting time for HTx was up to 12 months (6±5 months). There were no adverse, serious events (resuscitation, defibrillation for ventricular tachycardia (VT), intubation and ventilation, renal replacement therapy) up to 7 days after Lev infusion. Transient cardiac arrhythmias (ventricular bursts or non-sustained VTs) occurred in 11 patients (32%) with spontaneous termination and no need of urgent anti-arrhythmic therapy.
The values for sodium, potassium, Hb and CRP did not change significantly after Lev. In contrast, there was a significant reduction in creatinine after 4–8 days (initially 1.43±0.4 mg/dl; after 4–8 days 1.28±0.3; p&lt;0.0005) with an increase again after 14–20 days (1.43±0.3 mg/dl).
The bilirubin value was significantly reduced after 4–8 days (initially 1.63±0.7 mg/dl; after 4–8 days 1.30±0.5; p&lt;0.0005) with only partial (non-significant) increases again over the course (1.34±0.5 mg/dl). The BNP value was significantly reduced 4–8 days after administration of Lev (initially 1565±1136 ng/l; after 4–8 days 1103±895; p&lt;0.0001) and increased again in the longer time course (1462±1001 ng/l; p&lt;0.001 versus 4–8 days).
28 patients were successfully transplanted (82%). 6 patients remained without HTx (18%), of which 1 patient (3%) with clinical improvement could be discharged. 2 patients (6%) received an LVAD and 3 patients (9%) died during the waiting period.

Conclusion
Intermittent therapy with Lev as “a bridge to transplant” is safe and effective concerning deterioration of heart failure and prevention of progressive kidney/hepatic dysfunction. However, a prospective randomized multi-center trial is necessary to underscore the encouraging data of this observational, single center study.

Funding Acknowledgement
Type of funding sources: None.
Lipid profile in cardiac transplantation: a closer look at bad cholesterol
Authors: Alyaydin E , Pogoda C.A , Pistulli R , Lange S.A , Welp H , Dell Aquila A , Sindermann J , Reinecke H , Tuleta I 
Published: October 2021

Abstract

Background
When it comes to lipid-lowering therapy, the primary goal is still to reduce the low-density lipoprotein levels. Although remnant cholesterol (RC), including predominantly intermediate- and very-low-density lipoproteins, is a known cardiovascular risk factor, reliable reference values, as well as therapy strategies, are yet to be validated. Additionally, the role of RC after heart transplantation is still unclear.

Aim
To assess the clinical and prognostic relevance of lipid profile and, in particular, of remnant cholesterol in very long-term follow-up after HTx.

Methods
We performed a retrospective analysis of the clinical and laboratory parameters collected at last follow-up in an outpatient setting. Additionally, remnant cholesterol levels were estimated using the formula (in mg/dL): remnant cholesterol = total cholesterol – (HLD-C + LDL-C).

Results
Out of 174 patients with a mean age of 45.2±15.0 years at the time of HTx and a mean follow-up of 13.1±6.5 years, 142 (81.6%) were on statin treatment. Mean cholesterol level was borderline high (184.1±48.4 mg/dL), whereas mean LDL and triglyceride values were markedly elevated (103.6±39.2 and 161.8±83.8 mg/dL, respectively). HDL results were found to be 57.1±17.5 mg/dL. Statin treatment was associated with significantly lower LDL levels (124.6±53.5 vs. 98.8±33.6 mg/dL on statins, p=0.013), but failed to show prognostic relevance in a univariate cox-regression analysis (HR 0.79, 95% CI 0.37 – 1.72, p=0.57). RC was elevated in comparison to the background population with a mean level of 23.5±17.3 mg/dL (24.2±18.1 in male and 21.3±14.8 mg/dL in female) and a tendency for lower values when on treatment with statins but without statistical significance (28.5±19.2 vs. 22.3±16.8 mg/dL on statins, p=0.07). Treatment with higher doses of statins showed no relevant influence on the RC levels (p=0.62). Additionally, elevated RC was associated with higher C-reactive protein values as a sign of systemic inflammation (CRP &gt;0.5 mg/dL, OR 1.1, 95% CI 1.007 – 1.046, p=0.007). In a multivariate cox-regression analysis (adjusted for total cholesterol, LDL and triglycerides) RC was identified as a significant factor influencing mortality (HR 1.11, 95% CI 1.05 – 1.17, p&lt;0.001).

Conclusions
When addressing dyslipidaemia in heart transplantation, statin therapy can help reduce LDL levels, but this approach seems to be insufficient in achieving clinical benefit. Remnant cholesterol is a factor, which has proinflammatory properties and can potentially influence the prognosis in HTx. The possible therapeutic alternatives for this overseen component of the lipid profile are yet to be elucidated.

Funding Acknowledgement
Type of funding sources: None.
Early follow-up in the cardiological day hospital after heart surgery. Impact on hospital readmissions and emergency room visits
Authors: Vaqueriza Cubillo D , Gomez Mariscal E , Dominguez Munoa M , Beltran Herrera C , Suberviola Sanchez-Caballero V , Cano Moracho J.M , Giganto Arroyo M.L , Mora Yague L , Jimenez Loeches S , Sarrion Catala M.M , Cortina Camarero C , Cortes Beringola A , Gonzalez Pinto A , Cuerpo Caballero G , Munoz Aguilera R 
Published: October 2021

Abstract

Introduction
In the first few months after heart surgery, readmissions and emergency visits are common. In order to reduce these events, we developed an early follow-up protocol after discharge based on attention in our cardiological day hospital (CDH), which allows clinical and analytical assessment, monitoring and intravenous treatment at successive visits. The objective of the study is to assess the effectiveness of the protocol after its implementation.

Methods
Patients in our area discharged after heart surgery between 2013 and 2017 were included. They were divided into two groups, one with conventional follow-up and one with initial follow-up in CDH. Baseline clinical characteristics, type of surgery and surgical risk were compared. The primary endpoint was the time to the first readmission or emergency visit. The follow-up time was 200 days from discharge. Quantitative variables were compared using Student's t test and categorical variables using chi-square test. Cox proportional hazards model was used for multivariate analysis.

Results
321 patients, 160 with conventional and 161 with CDH follow-up, were included. There were no differences in baseline characteristics (age, type of surgery, comorbidities, risk and hospital stay) except for sex (44.7% women in conventional group vs 33.8% in HDC, p=0.04). The results of readmissions and the composite endpoint (readmission or emergency visit) at 30, 90 and 200 days are shown in the table. We found a trend of decreasing events in the CDH group, although statistical significance was not achieved. In multivariate analysis, the variables independently associated (p&lt;0.05) with an increase in the combined endpoint at 200 days were: female sex, prior atrial fibrillation, hypertension and an Euroscore surgical risk index greater than 3. The time to a first cardiological assessment after discharge decreased significantly in the CDH group (58 vs 18 days, p&lt;0.001).

Conclusions
In patients followed in CDH after heart surgery, there is a trend towards less readmissions and emergency visits in the first six months after discharge. Some baseline characteristics have been shown to be independently associated with the risk of events, which will help us to identify the most at-risk patients, on which an intervention could have a greater magnitude of benefit.

Funding Acknowledgement
Type of funding sources: None. Table 1. ResultsFigure 1. Hazard of composite end-point