bluuebunny/crossref_metadata_2025_split huggingface dataset:
The discongruence index, a simple predictor of cardiac remodeling after transcatheter aortic valve replacement
Authors: Islas F , De Agustin A , Jimenez P , Nombela L , Marcos Alberca P , Seabra D , Olmos C , Lepori A , Mahia P , Perez De Isla L 
Published: October 2021

Abstract

Background
Aortic stenosis causes several changes in left ventricular (LV) geometry and function; cardiac remodeling after transcatheter aortic valve replacement (TAVR) is variable among patients and it is not clearly defined. The aim of this study is to identify factors associated with LV functional and structural recovery.

Methods
428 patients were retrospectively studied; all patients underwent transthoracic echocardiography prior to TAVR; specific measurements such as maximum internal diameter of the prosthetic valve, nominal loss and percentage of nominal loss regarding to valve size, as well as the discongruence index (Prosthesis size/BSA) were evaluated at discharge and 1-year follow up. Positive cardiac remodeling (PCR) was considered if patients had a reduction of ≥20% of left ventricle mass index (LVMi) and ≥10% of end-diastolic volume index (LVEDVi).

Results
Mean age of the cohort was 83±5.6 years, 55% were female (n=236), mean aortic valve area was 0.7±0.2cm2; mean LVMi and LVEDVi were 129.4±35.4gr/m2 and 54.5±22ml/m2 respectively. LVMi reduction ≥20% was observed in 30% (n=128) of patients; LVEDVi reduction ≥10% was observed in 44% (n=188) of patients. A total of 107 patients (25%) showed PCR. Female patients showed more PCR (p=0.04). Discongruence index was significantly higher in patients with PCR (15.5±1.9 vs 14.5±1.8, p=0.01) and was significantly associated to LVMi (121.5±28.9 vs 150.8±41.1g/m2) and LVEDVi individually (55.1±17.2 vs 42.7±16.7ml/m2; p&lt;0.01). Left ventricular ejection fraction (LVEF) had a statistically significant increase among patients with PCR (53.2±14.9 vs 56.7±11.5, p=0.04) global longitudinal strain showed improvement at 1-year follow-up as well, although not statistically significant (−17.3±3.7 vs −18.3±3.4 p=0.53).

Conclusions
The discongruence index is a simple and feasible parameter that can predict positive cardiac remodeling after TAVR which can have a significant impact in clinical outcome of patients.

Funding Acknowledgement
Type of funding sources: None.
Machine learning analysis of metabolomic biomarkers for diagnosis of heart failure
Authors: Coorey C , Tang O , Yang J.Y.H , Figtree G 
Published: October 2021

Abstract

Background
There is emerging evidence that the pathophysiological mechanisms of heart failure are associated with alterations in serum metabolites. Such metabolomic signatures may be useful for heart failure diagnosis, stratification and prognosis.

Purpose
To evaluate the utility of including metabolomic biomarkers in addition to traditional cardiac biomarkers in a machine learning prediction model of heart failure diagnosis in the well-characterised Canagliflozin Cardiovascular Assessment Study (CANVAS) cohort.

Methods
A subgroup of the CANVAS/CANVAS-R study cohort was analysed. 101 metabolites in plasma were measured by HPLC (HILIC)-mass spectrometry. A 10-times 5-fold cross-validated support vector machine model with radial basis kernel function was constructed to predict heart failure diagnosis using traditional biomarkers alone and using the combination of traditional biomarkers and metabolomic biomarkers. Model performance and variable importance were both evaluated by area under the curve (AUC) of the receiver operating characteristics (ROC) curve. Results are shown as mean ± standard deviation.

Results
967 patients (of which 402 patients had heart failure) were included in the analysis with 341 females, mean age 63±8 years and mean body mass index (BMI) 33±5 kg/m2. All patients had diabetes mellitus with mean HbA1c 8.2±0.9%. The prediction model based on only traditional biomarkers had mean AUC 72±3% and the prediction model based on both traditional biomarkers and metabolomic biomarkers had mean AUC 80±3%. The top metabolomic biomarkers for predicting heart failure were threonine, L-homoserine, creatine and deoxyadenosine.

Conclusion
Metabolomic biomarkers improved diagnostic performance of a heart failure prediction model and captured variation not encompassed by traditional cardiac biomarkers.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Janssen Research and Development
Impact of right ventricular function and ventriculo-arterial coupling in prognosis after percutaneous edge-to-edge mitral repair
Authors: Gordillo X , Pozo Osinalde E , Salinas Gallegos A , Jimenez Quevedo P , Mahia P , Marcos-Alberca P , Tirado G , Luaces M , Macaya C , Perez-Villacastin J , Fernandez-Ortiz A , Nombela-Franco L , De Agustin J.A 
Published: October 2021

Abstract

Background
Left ventricular systolic function is widely used as selection criteria for appropriateness of percutaneous edge-to-edge mitral repair in patients with significant mitral regurgitation (MR) and high surgical risk. Although right ventricular (RV) systolic function and ventriculo-arterial coupling (VAC) have demonstrated its relevance in heart failure prognosis as well, few data are available regarding this procedure.

Purpose
To study the value of baseline RV function and VAC determined by transthoracic echocardiogram (TTE) on imaging and clinical prognosis.

Methods
We evaluated all the consecutive patients in which a percutaneous mitral edge-to-edge repair with the MitraClip system was performed between 2010 and 2020 in our tertiary university hospital. Baseline RV function was considered depressed if TAPSE &lt;16 mm, tissue Doppler S'&lt;9.5 cm/s or fractional area change (FAC) &lt;35% on TTE. VAC was calculated as ratio of TAPSE by pulmonary artery systolic pressure (PASP) from the same studies. Follow-up echocardiographic measurements were evaluated and clinical events were collected from medical records.

Results
We included 88 patients (64.8% males, 76±10 years) with MR grade ≥3. MR etiology was classified as functional 44.3%, organic in 35.2% and mixed in 20.5%. Previous to the procedure left ventricular systolic function was mildly depressed (LVEF 44.5±15.3%) and 33 patients (37.5%) showed an impaired RV systolic function. At 6 months TTE the prevalence of RV dysfunction lower to 27.3%. Patients with initial RV systolic dysfunction showed greater improvement in TAPSE (3.2 vs −0.53 mm; p=0.052) and FAC (8 vs 0.2%; p=0.016) at 6 months compared to those with normal baseline RV function. However, this variable was not associated with any relevant clinical event during the follow up. Baseline VAC demonstrated a significant inverse correlation with change in TAPSE (r −0.42; p=0.018), FAC (r −0.37; p=0.024) and S' (r −0.52; p=0.041) at 6 months. Among patients with initial RV impairment, VAC was lower in those who persisted with RV systolic dysfunction at 6 months (0.41 vs 0.49; p=0.054). Moreover, VAC was significantly associated with NYHA class ≥3 (0.48 vs 0.63; p=0.042) and cardiovascular hospitalization (0.53 vs 0.63; p=0.07), with a correlation with number of admissions (r −0.27; p=0.053).

Conclusion
In a percutaneous mitral edge-to-edge repair population previous presence of RV systolic dysfunction was not associated with clinical events during the follow up. Conversely, VAC was able to identify RV systolic function recovery and was associated with functional class and cardiovascular hospitalizations.

Funding Acknowledgement
Type of funding sources: None.
Estimation of possible candidates for ivabradine in rural Japan and investigation of their clinical characteristics
Authors: Saito M , Kinoshita M , Nakagawa H , Sumimoto T 
Published: October 2021

Abstract

Background
In Japan, ivabradine is indicated in patients with heart failure (HF) with sinus rhythm and a resting heart rate (HR) ≥75/min under standard treatment. Particularly, it is effective for HF with reduced left ventricular ejection fraction (LVEF). However, elderly people have a higher incidence of atrial fibrillation than young people, and their sinus node function is further deteriorated, resulting in a lower intrinsic HR. In addition, Japan is an ultra-aging society, especially in the countryside; therefore, the target patients for ivabradine may be limited in these regions.

Purpose
We sought to estimate the possible candidates for ivabradine and investigate their clinical characteristics in our hospital located in rural Japan.

Method and results
We retrospectively studied 14733 consecutive patients who were suspected heart disease who underwent echocardiography between January 2006 and October 2018 in Kitaishikai Hospital located in Ozu city (Proportion of the population aged ≥65 years: 34%, in 2015) and did not take ivabradine treatment. Of these, 187 patients with hemodynamically stable condition whose E/A ratio was measured and met the criteria of LVEF &lt;40% and HR ≥75 /min were confirmed. Of these, 153 patients reached HR &lt;75 /min with additional intensive medication within one year after the index echocardiography (Controlled group; mean HR: 82 to 62/min). The remaining 34 patients with uncontrolled HR (Uncontrolled group; mean HR: 84 to 82/min) were considered possible candidates for ivabradine (34/14733: 0.23%, 2.6 patients per year; median age, 74 years; male, 56%; median LVEF, 32%; ischemic cardiomyopathy, 53%). In the comparison of clinical and echocardiographic parameters in these two groups, Uncontrolled group had a significantly smaller left ventricular diastolic volume index (71 [59–85] vs 82 [66–109] /ml/m2, p=0.02), left ventricular systolic volume index (50 [39–59] vs 59 [42–80] / ml/m2, p=0.04), stroke volume index (22 [18–26] vs 26 [20–32] /ml/m2, p=0.02), left atrial volume index (47 [40–64] vs 59 [45–71] /ml/m2, p=0.02), and more hemodialysis (12 vs 3%, p=0.04) than Controlled group. However, the discrimination ability of these parameters for identifying Uncontrolled group was modest (Figure).

Conclusion
In rural Japan, possible candidates for ivabradine may be rare, so daily attention should be paid. Patients with reduced ejection fraction, small left ventricle, and hemodialysis may be the possible targets for this therapy.

Funding Acknowledgement
Type of funding sources: None.
Assessing the impact of cardiovascular events on health-related quality of life outcomes in DAPA-HF
Authors: McEwan P , Qin L , Jhund P.S , Docherty K.F , McMurray J.J.V 
Published: October 2021

Abstract

Background
Heart failure (HF) patients are at increased risk of cardiovascular (CV) events, including hospitalisation for HF (hHF), myocardial infarction (MI) and stroke, imposing a significant burden on health related quality of life (HRQoL). DAPA-HF was a multinational clinical trial (NCT03036124) investigating the efficacy and safety of dapagliflozin for the treatment of HF with reduced ejection fraction. Patient reported outcomes were collected. The objective of this study was to estimate the impact of CV events on patient HRQoL over time, as assessed through EQ-5D-5L and Kansas City Cardiomyopathy Questionnaire (KCCQ) total symptom score (TSS) and clinical symptom score (CSS).

Methods
Mixed effects regression models were developed based on pooled individual patient data from DAPA-HF to estimate the impact of hHF, MI and stroke on patient utility (EQ-5D-5L questionnaire responses weighted according to the societal value placed on given health states), and KCCQ TSS score. Utility was estimated using UK-specific tariffs after mapping EQ-5D-5L to EQ-5D-3L values in line with NICE guidance. A subject-specific intercept was incorporated, and estimates were adjusted for the incidence of events occurring within one month prior, two to four months prior, and 4 to 12 months prior to questionnaire completion.

Results
Mean patient baseline utility was 0.716 (95% CI: 0.711, 0.722), with KCCQ TSS 73.6 (73.0, 74.2). The incidence of CV events was consistently associated with reduced patient HRQoL, assessed through either EQ-5D or KCCQ TSS. In the first month following the event, hHF was associated with a 0.083 (0.06, 0.107) reduction in patient utility, and 16.9 (14.5, 19.4) reduction in KCCQ TSS (Fig. 1). Comparing measures, the disease specific measure KCCQ appeared more sensitive than EQ-5D to changes in HRQoL following hHF events and less sensitive to changes following MI and stroke events. Comparing events using the generic EQ-5D measure, at two months post-event, patients with MI and stroke returned to baseline utility; patients with hHF remained below baseline utility at each assessment point for 12 months (Fig. 2); where patients had a mean reduction of 0.02 (0.005, 0.035) utility and 0.5 (−1.1, 2.1) KCCQ-TSS compared to those without an hHF event.

Conclusion
The incidence of cardiovascular events imposes a considerable burden on HRQoL in patients with HFrEF. HF specific events may be better characterised with a disease specific tool, whereas for wider CV events a generic tool may be preferable. The impact of hHF on HRQoL was noteworthy in its persistence across the measures used up to one year. Interventions that reduce the risk of these events have the potential to significantly improve patient quality of life.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): AstraZeneca
Impact of polypharmacy on prognosis in patients with acute decompensated heart failure: from the CURE-HF registry
Authors: Kanai M , Motoki H , Okano T , Kimura K , Minamisawa M , Yoshie K , Kato T , Saigusa T , Ebisawa S , Okada A , Kuwahara K 
Published: October 2021

Abstract

Background
Polypharmacy would be associated with poor prognosis in patients with heart failure (HF).

Methods
In 863 patients who discharged after treatment for HF were prospectively enrolled. Number of tablets prescribed at discharge was counted. Death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for HF were tracked.

Results
In our study cohort (median age, 78), 447 patients experienced adverse events during median 503 days follow-up. In Kaplan-Meier analysis, a greater number of prescribed tablets was associated with future adverse cardiac events in the crude population. Although patients with the greater number of non-HF medications showed worse outcome, those of HF medications were not associate with the outcome (Figure). Furthermore, the number of tablets was an independent predictor of future cardiovascular events after adjustment for age, gender, B-type natriuretic peptide, hemoglobin, albumin, estimated glomerular filtration rate, and left ventricular ejection fraction (HR 95% CI: 1.295 (1.066–1.573), p=0.009).

Conclusions
Polypharmacy was associated with poor prognosis. Although the numbers of tablets and non-HF medications were significantly associated with worse out come in HF patients, the number of HF medications was not.

Funding Acknowledgement
Type of funding sources: None.
Elevated markers of liver function are associated with poorer outcomes in HFREF: an analysis of DAPA-HF
Authors: Cowan L , Adamson C , Docherty K , Inzucchi S , Koeber L , Kosiborod M , Martinez F , Ponikowski P , Sabatine M , Solomon S , Bengtsson O , Sjostrand M , Langkilde A , Jhund P , McMurray J 
Published: October 2021

Abstract

Background
Abnormalities of liver tests in patients with heart failure with reduced ejection fraction (HFrEF) is a well-recognised phenomenon. We examined the prognostic value of measures of liver function in a large contemporary cohort of patients with HFrEF enrolled in the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial

Methods
In this post-hoc analysis of the DAPA-HF trial we studied 4625 patients with liver function tests available at baseline. Cox proportional hazards models were used to assess the association between liver tests (total bilirubin, alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]) and the Model for End-stage Liver Disease excluding INR (MELD-XI) score (calculated as 5.11 Ln [total bilirubin as mg/dL] + 11.76 Ln [creatinine as mg/dL] + 9.44), and the risk of the primary composite endpoint (hospitalisation or urgent visit for heart failure or cardiovascular death). Models were adjusted for age, sex, race, region, systolic blood pressure, heart rate, LVEF, eGFR, log-transformed NT-proBNP, NYHA class, history of hypertension, stroke, myocardial infarction, atrial fibrillation, heart failure aetiology and randomized treatment to dapagliflozin and stratified by diabetic status at baseline. An interaction term between each measure and the effect of treatment on the primary composite outcome was tested as a fractional polynomial.

Results
Total bilirubin, ALP, and MELD-XI score were associated with a higher risk of all the primary outcome (Figure 1) but not ALT or AST. These relationships persisted after adjustment: total bilirubin per log unit increase (HR=1.46; 95% CI 1.28 – 1.67, p&lt;0.001), ALP per log unit increase (HR=1.39; 95% CI 1.15 – 1.66, p&lt;0.001), MELD-XI per 1 SD increase (HR 1.27; 95% CI 1.13 – 1.42, p&lt;0.001). The effect of dapagliflozin on the primary outcome was not modified by the baseline levels of either total bilirubin, ALP or MELD-XI score (Figure 2)

Conclusions
Higher total bilirubin, ALP and MELD-XI score were independently associated with a higher risk of cardiovascular death or worsening HF and may be useful routinely available biomarkers to assess prognosis. The efficacy of dapagliflozin was the not modified by baseline levels of any of these markers.

Funding Acknowledgement
Type of funding sources: None. Figure 2
Metformin improves diastolic dysfunction of non-diabetic patients with metabolic syndrome: the MET-DIME randomized trial
Authors: Santos-Ferreira D , Ladeiras-Lopes R , Sampaio F , Leite S , Vilela E , Leite-Moreira A , Bettencourt N , Gama V , Braga P , Fontes-Carvalho R 
Published: October 2021

Abstract

Background
Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including abdominal obesity, dyslipidaemia, arterial hypertension and abnormal glucose homeostasis, which occur together more frequently than by chance. Diastolic dysfunction (DD) is one of the most frequent manifestations of subclinical cardiac involvement of MetS, ultimately leading to heart failure with preserved ejection fraction. Metformin's new potential therapeutic actions include prevention of cardiac remodeling and fibrosis.

Purpose
We aimed to evaluate if metformin improves diastolic function (DF) in non-diabetic patients with MetS.

Methods
A prospective, randomized, open-label, blinded-endpoint trial was conducted over 24 months. Fifty-four non-diabetic adults with MetS and DD (defined as mean e'&lt;10.2cm/s or &lt;7.2cm/s for individuals 40–59 and 60–65 years old, respectively) were randomized to lifestyle counseling (control arm) or lifestyle counseling plus metformin (intervention arm) on a target dose of 1000 mg bid (figure 1). The primary endpoint was the change in mean e' velocity, assessed at 6, 12 and 24 months. Secondary endpoints included improvements in insulin resistance (HOMA-IR), functional capacity (peak oxygen uptake – VO2) and QoL (SF-36 score). Linear mixed effects modelling was used for longitudinal data analysis based on modified intention-to-treat (mITT) and per-protocol (PP) approaches.

Results
Forty-nine patients (mean age=51.8±6.4; 55% males) were included in the mITT analysis. Metformin use, on top of lifestyle counseling, led to an increase in mean e' velocity during follow-up (figure 2), with results at 24 months of +0.67±1.90cm/s (vs. −0.33±1.50cm/s in the control group, p=0.056), which reached statistical significance in PP analysis (+0.80±1.99cm/s vs. −0.37±1.52cm/s, p=0.039). In a random intercept linear mixed model adjusting for age, gender, treatment with drugs targeting the renin-angiotensin-aldosterone axis, presence of heart failure and baseline degree of DD, both mITT and PP analysis showed a statistically significant improvement of DF with metformin over time (β-coefficient=0.28, standard error (SE)=0.13, p=0.034, and β-coefficient=0.35, SE=0.14, p=0.011, respectively). This effect was independent of the observed reduction in insulin resistance. There were no differences regarding peak VO2 nor SF-36 score.

Conclusions
Treatment with metformin of non-diabetic MetS patients with DD, on top of lifestyle counseling, was associated with improved diastolic function.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Merck Study algorithmPrimary endpoint results
Early hospital trainings in patients with left ventricular mechanical support: influence on exercise tolerance and muscle strength
Authors: Smolis-Bak E , Chwyczko T , Zalucka L , Noszczak E , Bogucki M , Segiet-Swiecicka A , Piotrowicz R , Dabrowski R 
Published: October 2021

Abstract

Background
In extreme cases of heart failure, the only method of treatment is heart transplantation. Due to the insufficient number of organs for transplantation, left ventricular assist devices (LVAD) are increasingly being used. Rehabilitation of patients with LVAD is a very important element of complex therapy due to the long-term immobilization of these patients awaiting transplant or regeneration of the heart. The aim of the study was to assess the impact of early hospital rehabilitation on exercise tolerance, muscle strength and complex coordination in patients after LVAD implantation.

Material and methods
The study included 37 patients (35 men), aged 19–66 years, mean 58.7 years, after LVAD implantation. All of them underwent standard rehabilitation in the postoperative and rehabilitation department. The patients have started and continued trainings in a rehabilitation department for 4–5 weeks: endurance trainings, general fitness exercises with elements of balance and coordination exercises, elements of resistance exercises. Before the start of rehabilitation and after its completion, all patients underwent: cardiopulmonary exercise testing (CPET), a six-minute walk tests (6-MWT), the tests of strength of the right and left hand grip, strenght of muscles of the lower limbs and complex coordination (up and go test). There were no adverse events that would justify changing the mode or discontinuing rehabilitation.

Results
A significant increase in the value of most of the parameters studied was observed after the completion of hospital rehabilitation: VO2peak [ml/kg/min], baseline: 10.60 (9.60, 12.90) vs. 12.85 (11.60, 15.73), p&lt;0.001; 6-MWT [m]: 322.81 (113.62) vs. 416.12 (106.37), p&lt;0.001; 30 second chair stand: no of stands: 9.12 (3.60) vs. 11.18 (4.50), p&lt;0.001; up & go [sec] 9.18 (8.07, 10.50) vs. 7.58 (6.69, 9.04), p&lt;0.001; left hand grip strengh [kg]: 30.04 (8.38) vs. 31.91 (8.10), p&lt;0.011; right hand grip strengh [kg]: 31.52 (9.88) vs 33.20 (8.72), ns.

Conclusions
Early hospital rehabilitation in patients after implantation of left ventricular assist devices has significant benefits in terms of exercise tolerance, muscular strength and complex coordination. Complex rehabilitation is safe and effective in this group of patients.

Funding Acknowledgement
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): STRATEGMED II - RH-ROT - NATIONAL RESEARCH AND DEVELOPMENT CENTER