bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality based right ventricle functional echocardiographic cutoffs in patients with compared to without tricuspid regurgitation
Authors: Zornitzki L , Freund O , Frydman S , Rozenbaum Z , Granot Y , Banai S , Topilsky Y 
Published: October 2024

Abstract

Introduction
Tricuspid-annular-plane-systolic-excursion (TAPSE) and peak-lateral-tricuspid-annular-systolic-velocity (S’) are frequently used echocardiographic indices of right-ventricle (RV) function. Tricuspid regurgitation (TR) is present in 70-90% of the general population, and while trivial or mild TR may not have prognostic implications, several studies have demonstrated that ≥moderate TR is an independent predictor of adverse outcomes, and that increasing TR severity incurs an increased risk of mortality. The abnormality thresholds for TAPSE and S' are based on published mean and standard deviation data obtained from healthy adults, but not on outcome data. The effect of significant TR on the abnormality threshold of TAPSE and S’ prime is currently unknown.

Purpose
We aimed to re-examine the abnormality thresholds for TAPSE and S' based on their association with mortality in consecutive patients, stratified to with, or without, significant tricuspid regurgitation (TR).

Methods
We performed a retrospective analysis of consecutive patients undergoing echocardiography between 2011-2021 in a large tertiary center. TR was assessed using a semi-quantitative method. Cut-off values associated with excess mortality were assessed using spline curves in univariate, and multivariate Cox logistic regression analyses.

Results
A total of 24717 subjects were included in the current analysis with a median (interquartile range) follow up of 1321 (581-1902) days. 1143 (4.6%) subjects had clinically significant (≥moderate) TR. In the entire cohort, TAPSE&lt;20.9 mm and S’ &lt;10.9 cm/s were associated with excess mortality. In sub-group analysis, among subjects with significant TR, TAPSE&lt;18.0 mm and S'&lt;10.0 cm/s was the cutoff associated with excess mortality, while subjects without TR had a higher cutoff of TAPSE&lt;21.5 mm and S'&lt;10.9 cm/s. In a multivariate model adjusted for the presence of TR and baseline characteristics, TAPSE&lt;20.9 mm (HR 1.20, 95% CI 1.14-1.27; p&lt;0.001) and S’&lt;10.9 cm/s (HR 1.07, 95% CI 1.01-1.13; p=0.015) were independent predictors for mortality. A sensitivity analysis, which included 14,664 patients with additional echocardiographic indices, demonstrated that low TAPSE remained an independent predictor of mortality (aOR=1.15; 95% CI: 1.07-1.24; p&lt;0.001)

Conclusion
TAPSE and S’ thresholds associated with excess mortality are higher than those previously reported in healthy adults. The TAPSE and S' cutoffs associated with excess mortality were lower in patients with significant TR compared to patients without, suggesting that a personalized approach for their interpretation is needed.Central illustration
Effects of Sacubitril/Valsartan on all-cause hospitalizations in heart failure: participant-level pooled analysis of PARADIGM-HF and PARAGON-HF
Authors: Lu H , Claggett B L , Packer M , Lam C S P , Swedberg K , Rouleau J , Zile M R , Lefkowitz M , Desai A S , Jhund P , Mcmurray J J V , Solomon S D , Vaduganathan M 
Published: October 2024

Abstract

Background
Sacubitril/valsartan is indicated to reduce the risk of cardiovascular (CV) death and heart failure (HF) hospitalizations in patients with chronic HF. However, many of these patients are older and have multiple comorbidities that increase the risk of hospitalizations other than HF, yet the effects of sacubitril/valsartan on hospitalizations of any cause have not been well described.

Methods
PARADIGM-HF and PARAGON-HF were phase-3, global multicenter randomized clinical trials that evaluated sacubitril/valsartan versus enalapril (in PARADIGM-HF) or valsartan (in PARAGON-HF) across the spectrum of left ventricular ejection fraction (LVEF; ≤40% in PARADIGM-HF and ≥45% in PARAGON-HF). We pooled individual participant-level data from these 2 trials to examine the effects of sacubitril/valsartan on time-to-first investigator-reported all-cause and cause-specific hospitalization using Cox proportional hazards models, stratified by geographic region and trial. We additionally examined heterogeneity in treatment response by LVEF.

Results
Over 2.8 years median follow-up, among 13,194 participants in the pooled PARADIGM-HF/PARAGON-HF, sacubitril/valsartan significantly reduced the risk of all-cause hospitalizations compared with renin-angiotensin system inhibitor (HR 0.92; 95% CI 0.88-0.97; P=0.002); Figure 1 Panel A. The absolute risk reduction (ARR) was 2.1 per 100 patient-years corresponding to a number-needed-to-treat (NNT) of 48 patient-years of treatment exposure to prevent 1 all-cause hospitalization. Reductions in overall hospitalizations among patients with identifiable causes (N=5,783) seemed to be primarily driven by lower rates of cardiac and pulmonary hospitalizations associated with sacubitril/valsartan. Patients treated with sacubitril/valsartan did not have a higher rate of composite non-cardiac hospitalizations (Figure 1 Panel B). Similarly, sacubitril/valsartan reduced the risk of the composite of all-cause hospitalization or all-cause mortality (HR 0.92; 95% CI 0.87-0.96; P&lt;0.001), with an ARR of 2.5 per 100 patients-years and an NNT of 40 patient-years. For all-cause hospitalization, we observed significant heterogeneity by LVEF as a continuous measure (Pinteraction=0.027); treatment effects were most apparent in those with an LVEF below 60% (HR 0.91 95% CI 0.86-0.96; Figure 2).

Conclusions
In a pooled analysis of &gt;13,000 patients with chronic HF, sacubitril/valsartan reduced hospitalization for any reason with benefits most apparent among those with an LVEF below normal.
The effects of SGLT2 inhibitors on right ventricle functions in heart failure patients: update meta-analysis of the current literature
Authors: Cinar T , Saylik F , Cicek V C , Pay L , Khachatryan A , Alejandro J , Erdem A , Hayiroglu M I 
Published: October 2024

Abstract

Background
There is some discrepancy in the present studies concerning the effect of sodium-glucose cotransporter type 2 (SGLT2) inhibitors on right ventricular (RV) functions in heart failure (HF) patients. The current meta-analysis was focused on determining the impact of SGLT2 inhibitors on RV functions in such individuals.

Methods
Two independent investigators searched PubMed, Google Scholar, and the Cochrane Library for articles of interest. To analyze heterogeneity, Higgins' I2 as well as prediction intervals and Egger's test were utilized to assess heterogeneity. The Newcastle-Ottawa standard ratings approach was used to assess the quality of observational studies. The Robin-I risk of bias algorithm was used to assess the bias risks of randomized studies.

Results
This meta-analysis evaluated 8 studies in total. Over the follow-up time frame, patients who used SGLT-2 inhibitors had substantially lower systolic pulmonary artery pressure (sPAP) and higher TAPSE values (mean difference (MD) = 1.30 [0.78;1.82], p =0.002 and MD =-5.39 [-7.88; -2.89], p=0.003, respectively). There was no significant difference in RVS’ values between follow-up and baseline (MD=1.38 [-1.35;3.80], p=0.169). However, as compared to the baseline period, fractional area contraction (FAC) values were substantially larger at the end of the follow-up period (MD=5.40 [3.74;7.07], p=0.015).

Conclusion
To the best of our knowledge, this is the first meta-analysis assessing the impact of SGLT2 inhibitors on RV function in HF patients. Our findings suggest that SGLT2 inhibitors may improve RV performance in HF patients.
Prognostic and diagnostic implications of impaired rest and exercise-stress left atrial compliance in heart failure with preserved ejection fraction: Insights from the HFpEF Stress Trial
Authors: Backhaus S J , Schulz A , Lange T , Schmidt-Schweda L S , Hellenkamp K , Evertz R , Kowallick J T , Kutty S , Hasenfus G , Schuster A 
Published: October 2024

Abstract

Background
With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress right heart catheterisation is well established, the clinical routine struggles between feasibility of exercise-stress and diagnostic accuracy of available tests.

Methods
The HFpEF Stress Trial (DZHK-17) prospectively enrolled 75 patients with exertional dyspnoea and echocardiographic signs of diastolic dysfunction (E/e’&gt;8) who underwent simultaneous rest and exercise-stress echocardiography and RHC. HFpEF was defined according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥15mmHg stress: ≥25mmHg). Patients were classified as non-cardiac dyspnoea (NCD) in the absence of HFpEF and cardiovascular disease. LA compliance was defined as reservoir strain (Es)/(E/e’). Follow-up was conducted after 4 years to evaluate cardiovascular hospitalisation (CVH).

Results
The final study population included 68 patients (HFpEF n=34 and NCD n=34) of which 23 reached the clinical endpoint, 1 Patient was lost to follow-up. Patients with HFpEF according to the HFA-PEFF score (≥5 points) had significantly lower LA compliance at rest (p&lt;0.001) compared to patients with a score ≤4. LA compliance at rest outperformed E/e’ (AUC 0.78 vs 0.87, p=0.024) and showed a statistical trend to outperform Es (AUC 0.79 vs 0.87, p=0.090) for the diagnosis of HFpEF. LA compliance at rest predicted CVH (HR 2.83, 95% CI 1.70-4.74, p&lt;0.001) irrespective of concomitant atrial fibrillation.

Conclusions
LA compliance at rest can be obtained from clinical routine imaging and bears strong diagnostic and prognostic accuracy. Addition of LA compliance can improve the role of echocardiography as the primary test and gatekeeper.
Disease-modifying treatments in transthyretin amyloid cardiomyopathy: a meta-analysis of randomized controlled trials
Authors: Tsai C H , Kao T W , Lin Y H 
Published: October 2024

Abstract

Background and Aims
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and life-threatening disease. With advancements in pharmacology, numerous novel medications are currently under investigation. However, the effects of these treatments on long-term outcomes remain elusive and inconclusive.

Methods
PubMed, MEDLINE, Embase, and the Cochrane Library were searched for literature inclusion until January 2024. Only phase 3, high-quality, randomized controlled trials related to ATTR-CM were considered for enrolment. Endpoints included all-cause mortality, six-minute walk distance, Kansas City Cardiomyopathy Questionnaire–Overall Summary Score, and serum N-terminal pro-B-type natriuretic peptide (NTproBNP) levels. A random-effects model was applied for meta-analysis.

Results
Three landmark trials (ATTR-ACT, APOLLO-B, ATTRibute-CM) comprising 866 patients with ATTR-CM were pooled. 66.6% of the subjects were administered with medical treatment. Consistent improvements in all-cause mortality (P=0.001), 6-minute walk distance (P=0.045), Kansas City Cardiomyopathy Questionnaire–Overall Summary Score (P&lt;0.001), and serum NTproBNP level (P=0.002) were present by medical treatment. At 12 months, only NT-proBNP showed significant improvement in the pooled analysis of the APOLLO-B and ATTRibute-CM results. At 30 months, the pooled analysis of ATTR-ACT and ATTRibute-CM demonstrated significantly better all-cause mortality and KCCQ scores in patients received mediation.

Conclusions
Disease-modifying Treatments is associated with better survival, functional capacity, quality of life, and NTproBNP level in patients with ATTR-CM. Extended follow-up duration might be needed to demonstrate efficacies.
Effects of Dapagliflozin on myocardial performance in non-diabetic patients with Heart failure with reduced and mid-range ejection fraction (DAPA ECHO trial)
Authors: Pastore M C , Stefanini A , Mandoli G E , Piu P , Iuliano M A , Diviggiano E E , Carli L , Marchese A , Pecere A , Martini L , Cavigli L , Focardi M A , D'ascenzi F , Valente S , Cameli M 
Published: October 2024

Abstract

Background
Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE).

Methods
This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints.

Results
Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p&lt;0.0001), indicating a significant difference between dapagliflozin and OMT.

Conclusions
This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.
Effect of Dapagliflozin on health-related quality of life in patients with heart failure: a meta-analysis of Randomized Controlled Trials
Authors: De Souza M , Rodrigues Defante M L , Martins Prizao V , Consendey Martins O , Morais B , Ximenes Mendes B , Muniz J 
Published: October 2024

Abstract

Introduction
Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces the risk of cardiovascular mortality and hospitalization for heart failure among individuals with chronic heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF). The effect of dapagliflozin on symptoms, physical capacity and quality of life is still unclear in this population.

Purpose
To investigate the effects of dapagliflozin on symptoms and health-related quality of life improvement in patients with chronic heart failure.

Methods
We systematically searched PubMed, Embase and Cochrane Central databases for randomized controlled trials (RCTs) comparing dapagliflozin to placebo in patients with chronic heart failure. We pooled mean differences (MD) and 95% confidence intervals (CI) with a random-effects model for continuous outcomes. Subgroup analyses were performed by reduced or preserved ejection fraction (EF). The outcomes analyzed were change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score and six-minute walk test (6MWT).

Results
Five RCTs with 6,238 patients were included. Of these, 5,410 (86.7%) presented a reduced EF and 2,724 (43.65%) had diabetes. There was a statistical significant improvement in total symptoms score (KCCQ-TSS) (MD=3.08; 95% CI 2.14-4.02; p&lt;0.00001; I2=0%; Fig.1A) and in physical limitation score (KCCQ-PLS) (MD=3.91; 95% CI 1.66-6.17; p=0.0007; I2=0%; Fig1B) when dapagliflozin was compared to placebo. Subgroup analyses showed that the KCCQ-TSS score were significant higher in patients treated with dapagliflozin when compared to placebo in HFrEF (MD= 2.98; 95% CI 1.96-.99; p&lt;0.00001; I2=0%; Fig1A) and HFpEF group (MD=3.73; 95% CI 1.16-6.30; p=0.004; I2=0%; Fig1A). The KCCQ-PLS score had a significant increase after dapagliflozin treatment when compared to placebo in participants with HFrEF (MD=4.36; 95% CI 0.72-8.00; p=0.02; I2=0%; Fig1B) and HFpEF (MD=3.64; 95% CI 0.76-6.51; p=0.01; I2=0%; Fig1B). There was no significant difference in 6MWT in dapagliflozin versus placebo group (MD=5.78; 95% CI -0.48-12.03; p=0.07; I2=0%; Fig.2).

Conclusions
Dapagliflozin improves health-related quality of life by reducing symptoms and physical limitation in patients with HFrEF and HFpEF.
Predictors of hypercontractile heart phenotype in patients with chronic coronary syndromes
Authors: Wang Y , Cerracchio E , Ciampi Q , Cortigiani L , Zagatina A , Kasprzak J D , Wierzbowska-Drabik K , Boshchenko A , Gaibazzi N , Djordjevic-Dikic A , Pitino A , Tripepi G L , Citro R , Pellikka P A , Picano E 
Published: October 2024

Abstract

Background
Hypercontractile phenotype of the left ventricle (LV) is an actionable therapeutic target in patients with chronic coronary syndromes (CCS), but its clinical recognition remains elusive.

Purpose
To assess the clinical variables associated with the hypercontractile phenotype of the LV, identified with supernormal values of an index of LV contractility such as LV force, also known as ventricular elastance.

Methods
In a prospective, observational, multicenter study, we recruited 5,122 patients (age 65± 11.1 years, 2974 males, 58%) with CCS referred for resting transthoracic echocardiography with technically successful volumetric echocardiography in 17 accredited laboratories. We measured systolic blood pressure (SBP) with a cuff sphygmomanometer. We assessed semi-quantitatively wall motion score index (WMSI), and quantitatively LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), force (SBP/ESV), stroke volume (SV), arterial elastance (SBP/SV), ventricular-arterial coupling (VAC, as SV/ESV), and cardiac output (CO = SV*heart rate).Univariable and multivariable logistic regression analysis assessed independent factors associated with the highest force sextile. Odds ratios (ORs) with the corresponding 95% conﬁdence interval (CI) were estimated.

Results
For all the studied patients, EF was 59±11%. Force was 4.51±2.11 mmHg/ml, with reference sextile = 3.50-4.26 mmHg/ml, lowest sextile (Group 1) &lt;2.60 mmHg/ml and highest sextile (Group 6) &gt; 6.36 mmHg/ml. The correlation between the log of EF and the log of Force was significant with linear regression (r = 0.73, p &lt; 0.001). Patients in the highest sextile of force showed lower values of WMSI, SV, EDV, and ESV, and higher values of arterial elastance and VAC (Table). By multivariable logistic regression model, the highest sextile of force was associated with age &gt; 71 years (OR 4.35, 95% CI 3.06-6.18, p &lt; 0.001), female sex (OR 4.48, 95% CI 3.62-5.54, p &lt; 0.001), absence of beta-blocker therapy (OR 1.56, 95% CI 1.27-1.91), rest SBP&gt; 159 mmHg (OR 6.86, 95% CI 5.03-9.35, p &lt; 0.001), high heart rate (OR 1.03, 95% CI 1.02-1.04, p &lt; 0.001), absence of prior MI (OR 1.31, 95% CI 1-1.72, p = 0.049), and higher LV EF at rest (OR 1.24, 95% CI 1.22-1.26, p &lt; 0.001).

Conclusions
A hypercontractile phenotype of the LV with high force is associated with a small heart, reduced SV, and higher arterial elastance. It was clinically associated with advanced age, female sex, history of hypertension, absence of beta-blocker therapy, and high resting SBP.
Urinary proteomic signature of mineralocorticoid receptor antagonism by spironolactone: evidence from the HOMAGE trial
Authors: Yu Y L , Gonzalez A , Hansen T W , Verdonschot J A J , Ahmed F , Petutschnigg J , Heymans S , Girerd N , Clark A L , Cleland J G , Zannad F , Diez J , Mischak H , Ferreira J P , Staessen J A 
Published: October 2024

Abstract

Background
Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) detects many sequenced peptides, for &gt;70% derived from collagens.

Purpose
UPP and serum fibrosis markers were analysed together in patients at risk of HF with as objective to generate insights into the antifibrotic action of spironolactone.

Methods
In the open-label HOMAGE trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/d and followed for 9 months (n=290; 23.8% women; median age: 73 years). UPP was done by capillary electrophoresis coupled with mass spectrometry; 1498 urinary peptides with detectable signal in ≥30% of patients were analysed. Serum markers of COL1A1 synthesis (PICP and PICP/CITP) were measured. After rank normalisation of the biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted models. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher Z transform.

Results
Among all the urinary peptides, only the changes in collagen fragments remained significantly different (p&lt;0.05) between randomisation groups after accounting for baseline levels, covariables and multiple testing. Compared to the control group, spironolactone reduced 16 of 27 collagen-derived urinary peptides. From baseline to 9 months, serum PICP and the PICP/CITP ratio decreased from 79.0 to 75.4 µg/L and from 21.3 to 18.3, respectively (p≤0.0129), reflecting decreased COL1A1 synthesis. Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and the serum fibrosis markers.

Conclusions
Spironolactone downregulated urinary collagen-derived peptides, probably by shrinking the body-wide pool of collagens. Spironolactone did not affect the interaction between urinary and serum fibrosis markers, suggesting that collagen scaffolding is maintained, thereby explaining why some urinary collagen fragments increased. Combining urinary and serum fibrosis biomarkers opens new avenues for discovery of antifibrotic drugs and refines insight in the action of antifibrotic drugs.Figure 1Figure 2