Outcomes In Heart Failure Patients Research Articles

Abstract 4119908: Outcomes for heart failure patients with reduced ejection fraction attending emergency department and discharged within 24 hours versus those admitted patients in heart failure unit.

Introduction: Heart failure (HF) is a clinical syndrome with increasing prevalence. Currently, there are extensive evidence-based therapies targeted at managing patients with heart failure and reduced ejection fraction (HFrEF) to improve outcomes. The National Heart Failure Audit shows the quality of inpatient care (specialist review, discharge medication etc) is related to outcome. This study aimed to evaluate the current practice at a London tertiary centre hospital in managing patients with heart failure and compared outcomes in patients who had a short course of admission (less than 1 day) with those who had a more prolonged course of admission. Method: Retrospective data was collected from a London tertiary centre hospital database for consecutive patients from Sep/2022 till Sep/2023. Statistical analysis was performed using Chi-Square test. The eligibility criteria included a new or previous diagnosis of HF with left ventricular ejection fraction (LVEF) < 40%. Patients were divided into two groups: Group A included 40 eligible patients who were admitted and discharged from the emergency department (ED) within 24 hours. Group B included 37 eligible patients who were admitted and discharged from the dedicated heart failure unit after 10-15 days of hospital admission. Results: In Group A, prescribing guideline-directed medical therapy (GDMT) was lower compared to Group B; Renin-Angiotensin-Aldosterone Inhibitors (47.50% vs. 94.59%), beta blockers (55% vs. 91.89%), mineralocorticoid receptor antagonists (12.50 %vs. 94.59%), and sodium-glucose co-transporter 2 inhibitors (15% vs. 89.19%). More patients in Group B received all four pillars of GDMT (86.49%) compared to Group A (5%). At 6-month follow-up,18.75% were on 4 GDMT in Group A versus 92% in group Group B. Re-admission within 6 months was higher in Group A (30%) compared to Group B (16.22%); however, the difference was not statistically significant (P value: 0.153). Higher mortality rates were observed in Group A (mortality rate: 20%) compared to Group B (mortality rate: 2.70%), with statistical significance (P value: 0.018). Conclusion: This study showed that HFrEF patients admitted to a specialist heart failure unit achieve higher rates of GDMT and have significantly improved outcomes compared to those who had a shorter inpatient stay and discharged from the emergency department. These findings underscore the high risks associated with rapid discharge from hospital on incomplete medical therapy.

Abstract 4145889: Association between Pulmonary Artery Elastance and all cause mortality in patients with Heart Failure: A Meta-Analysis

Background: Pulmonary Artery Elastance (PAE) is an echocardiographic value commonly calculated in Heart Failure (HF) patients. It is presumed to be associated with mortality and adverse outcomes. We aim to evaluate pulmonary artery elastance (PAE) as a predictor of all-cause mortality in heart failure (HF) patients Methods: A comprehensive literature review was conducted on PubMed and Google Scholar from inception till May 2024 for articles relevant to the mortality outcomes in HF patients with respect to pulmonary arterial elastance as one of their predictors. Data were extracted independently by four different reviewers. We used a fixed-effects model meta-analysis model to evaluate and pool the outcomes in association with PAE and all-cause mortality. Further assessment of the outcomes was performed by sensitivity analysis with a one-study removal method and meta-regression analysis. Results: Out of 63 studies, 4 studies with 759 patients were included in our meta-analysis. Mean age ranged from 54 to 65 years. We found there was a statistically significant association between pulmonary artery elastance and all-cause mortality (OR: 1.12, 1.06 - 1.19, p < 0.0001] (Figure 1a). Sensitivity analysis with one-study removal showed overall effects in the meta-analysis still lean towards supporting PAE as the predictor for ACM (Figure 1b). Meta-regression analysis with age (Figure 1c), sex and other supportive variables did not show statistically significant associated confounders. Conclusion: This meta-analysis establishes a significant association between elevated PAE and increased risk for all-cause mortality in HF patients. These results suggest PAE could be a strong predictor for all-cause mortality in HF patients. Further research is needed to provide a more comprehensive understanding of the predictive value of PAE for HF patients. The association between PAE and mortality could provide significant insights that could influence clinical practice and improve patient outcomes in HF.

Abstract 4113885: Impact of Sodium-glucose Cotransporter 2 Inhibitor on Recurrence and Cardiovascular Outcomes after Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure

Background: Catheter ablation for Atrial fibrillation (AF) has been proven to improve the prognosis in patients with heart failure (HF), while it remains a high risk for AF recurrence and adverse cardiovascular outcomes. The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in HF patients after AF ablation is unknown. Method: HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups based on the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n=368) and non-SGLT2i using (n=368) in each group. The primary outcome was AF recurrence after a 3-month blanking period. Results: During a total of 1315 person-year follow-ups, AF recurrence occurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted HR = 0.56, 95% CI: 0.43-0.74, P<0.001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted HR = 0.58, 95%CI: 0.41-0.80, p = 0.001). Although there was a tendency towards benefits, significant differences in all-cause mortality (adjusted HR = 0.76, 95%CI: 0.35-1.63, p = 0.480), cardiovascular mortality (adjusted HR = 0.62, 95%CI: 0.24-1.57, p = 0.312) and thrombotic events (adjusted HR = 0.40, 95%CI: 0.16-1.03, p = 0.056) were not noted between groups. Conclusion: The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF.

Abstract 4135289: Renal Blood Perfusion is Closely Related to Right Ventricular Volume Overload in Congestive Heart Failure

Background: Cardiorenal syndrome (CRS) involves a bidirectional relationship where dysfunction in one organ exacerbates the other. A key factor in this interaction is the impact of right ventricular (RV) volume overload on renal blood flow, which is vital for the progression and management of heart failure (HF). Objective: This study aims to explore and quantify the relationship between right ventricular volume overload, i.e, echocardiographic assessments of right ventricular diameter (RVD), and the time-to-peak (TTP) of renal blood flow in patients with HF measured by 99mTc-DTPA renal scintigraphy. Methods: This single-center study included 304 stable, ambulatory HF patients admitted between October 2017 and August 2022. HF was diagnosed based on the 2016 ESC guidelines. Echocardiographic parameters, including RVD, and TTP of renal blood flow measured by 99mTc-DTPA renal scintigraphy, were collected. Statistical analysis was conducted using SPSS and R software, with Spearman correlation analysis used to assess the relationship between echocardiographic parameters and TTP. Results: The study showed there was a significant correlation between RVD and TTP (rs=0.535, P <0.001), indicating that RV volume overload is closely related to impaired renal perfusion. The median TTP among the study population was 27.25 seconds (IQR: 21-39 seconds). Corrected for body surface area (BSA), RVD was found to be significantly higher in patients with heart failure with reduced ejection fraction (HFrEF) compared to heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF) (HFrEF: 20.62 mm/m 2 , HFmrEF: 18.72 mm/m 2 , HFpEF: 18.09 mm/m 2 ; p < 0.001). Furthermore, right atrial diameter (RAD) corrected for BSA (RAD/BSA) demonstrated the strongest correlation with TTP in the HFrEF subgroup (rs=0.602, p<0.001). Conclusions: Our findings highlight the significant impact of right ventricular volume overload on renal perfusion, providing valuable insights into the pathophysiology of CRS. These results suggest that therapeutic strategies aimed at reducing RV overload could enhance renal perfusion and improve overall outcomes in HF patients.

Advancing Heart Failure Treatment: The Role of Multipoint Pacing in Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) with biventricular pacing is a standard therapy for patients with heart failure, reduced ejection fraction, and electrical dyssynchrony. However, approximately 30% of patients do not respond to CRT. Multipoint pacing (MPP) has emerged as an innovative strategy that paces multiple left ventricular sites to achieve more comprehensive resynchronization. This review explores the evolution of MPP, including the underlying scientific rationale, clinical evidence from key trials, technological considerations of quadripolar leads and programmability, patient selection criteria, optimization strategies, and future directions. Early feasibility studies demonstrated acute hemodynamic improvements with MPP. Larger trials have shown superior outcomes with MPP compared to conventional biventricular pacing, including increased CRT response rates, reduced hospitalizations, and improved ejection fraction and reverse remodeling. However, recent multicenter trials found no significant differences between the population's MPP and biventricular pacing. Ongoing research aims to refine patient selection for MPP and optimize lead positioning and programming configurations to maximize benefits. As technological capabilities expand, MPP promises to provide tailored, physiological pacing therapies that may enhance outcomes for heart failure patients requiring CRT. This comprehensive review examines the various aspects of MPP, including its scientific foundation, clinical evidence, technological considerations, impact on patient quality of life, and future implications. By critically assessing the current literature and identifying gaps in knowledge, we aim to provide a thorough understanding of MPP’s role in the evolving landscape of heart failure management.

The Role of Cardiac Magnetic Resonance to Predict Response to Cardiac Resynchronization Therapy: A Systematic Review and Meta-analysis.

Cardiac resynchronization therapy (CRT) has revolutionized heart failure (HF) management, offering benefits in morbidity, mortality, and symptom alleviation. However, optimal response rates are not universally achieved, necessitating enhanced patient-selection strategies. Myocardial scar patterns, quantified by delayed-enhancement cardiac magnetic resonance (DE-CMR), have been implicated in CRT outcomes. We conducted a meta-analysis of observational studies assessing CRT responses by performing a systematic literature search using PubMed, Embase, Ovid MEDLINE, Scopus, the Cochrane Library, ScienceDirect, and the Web of Science. Scar burden, left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) were evaluated. CRT response rates among ischemic and non-ischemic cardiomyopathy patients were also explored. This meta-analysis incorporated eight studies meeting the eligibility criteria. CRT responders exhibited a significantly lower scar burden (-11.7%; 95% confidence interval, 6.6%-16.8%) compared to non-responders, supporting the predictive value of scar quantification (I 2 = 95.25%; P < .001). Responders demonstrated an increased mean LVEF (from 25.2% to 31.9%), while non-responders showed modest changes (from 23.3% to 24.4%). Responders experienced a decrease in mean LVESV from 158.8 to 132.8 mL, contrasting with a more stable mean LVESV value in non-responders (reduction from 160.9 to 157.6 mL). Responders experienced a reduced mean LVEDV from 219.4 to 196.7 mL, while non-responders showed more minimal changes (from 213.4 to 210.6 mL). Limited data suggested a CRT response rate of 34.7% in ischemic cardiomyopathy; non-ischemic data were insufficient. In conclusion, DE-CMR, assessing the scar burden, emerges as a valuable tool for predicting the CRT response. A lower scar burden correlates with improved responses, supporting the role of DE-CMR in refining patient selection for CRT. This meta-analysis contributes insights into personalized CRT strategies, emphasizing the potential of imaging modalities to enhance therapeutic outcomes in HF patients. Further research is warranted to solidify these findings and refine clinical applications.

Association of BMI with adherence and outcome in heart failure patients treated with wearable cardioverter defibrillator.

Obesity is a known risk factor for cardiovascular disease (CVD), yet an 'obesity paradox' has been observed in various CVD contexts. The impact of obesity on heart failure (HF) patients treated with a wearable cardioverter-defibrillator (WCD) remains underexplored. In a multicentre international registry, we retrospectively collected data from a consecutive series of 1003 patients. These patients were divided into three body mass index (BMI) groups: <25kg/m2 (n=348), 25-30kg/m2 (n=383), and >30kg/m2 (n=272), with BMI>30kg/m2 defined as the reference category. Demographics, indications, adherence, WCD shocks, arrhythmic events, rehospitalization due to cardiovascular causes, and mortality were analysed. At 3month follow-up, patients with a BMI>30 showed the greatest improvement in left ventricular ejection fraction (LVEF) at 51.4%, significantly higher than the 41.4% in those with a BMI<25 (P=0.017) and comparable with the 49.4% in the BMI 25-30 group (P=0.635). WCD wearing time and adherence were similar across all BMI groups. The incidence of WCD shock was similar across BMI groups. Rates of ventricular tachycardia (VT), ventricular fibrillation and non-sustained VT (ns-VT) were comparable across BMI groups. The rate of implantable cardioverter-defibrillator (ICD) implantation was 40.3% across all patients, with a slightly lower rate in the BMI>30 group (36.8%) compared with others, although not significantly. Rehospitalization due to cardiovascular causes was significantly lower in the BMI>30 group (55.4%) compared with the BMI 25-30 group (70.9%; P=0.048), but similar to the BMI<25 group (54.9%; P=0.957). At 2year follow-up, mortality was lower in the BMI>30 group (5.9%) compared with the BMI<25 (7.5%; P=0.029) and BMI 25-30 groups (7%; P=0.681). In multivariable analysis, LVEF at long term was significantly associated with a reduction in mortality. Obese patients exhibited significantly greater improvement in LVEF, which was associated with reduced mortality. Adherence to WCD therapy was excellent across all BMI groups. ICD implantation occurred in 40.3% of patients, with similar WCD shock rates and arrhythmic events across BMI groups. An obesity paradox was observed, with obese patients demonstrating significantly lower rehospitalization rates due to cardiovascular causes and reduced mortality at follow-up.

Temporal trends in clinical outcomes in heart failure patients with and without atrial fibrillation: a nationwide study from 1997-2018

Abstract Background Given the many advances in treating heart failure (HF) and atrial fibrillation (AF) separately over the past decades, it remains unclear how the prognosis of patients diagnosed with both conditions has changed over time. Purpose We aimed to investigate the temporal trends in all-cause mortality, HF hospitalisation, and stroke from 1997 to 2018 in patients diagnosed with both HF and AF. Methods From Danish nationwide registries, we identified 152,059 patients with a first-time HF-diagnosis from 1997 to 2018. Patients were categorised into groups based on their AF status: prevalent AF (n=34,734), new-onset AF (n=12,691), and absence of AF (n=104,634). Patients were further subdivided into four year groups (1997-2001, 2002-2006, 2007-2012, 2013-2018), based on the year of HF onset. The primary outcome of interest was the absolute five-year risk of all-cause mortality, and key secondary outcomes were HF hospitalisation and stroke, investigated using the Aalen-Johansen estimator, accounting for competing risk of death. Results Between 1997 and 2018 the proportion of patients with new-onset HF and prevalent AF increased from 17.0% (n = 6,372) to 27.7% (n = 11,569), while those with concurrent new-onset AF increased from 7.7% (n = 2,884) to 8.1% (n = 3401). Contrary, the proportion of patients decreased among those with no AF from 75.3% (n = 28,235) to 64.2% (n = 26,850). The five-year risk of all-cause mortality decreased from 69.1% (95% CI): 67.9%-70.2%) to 51.3% (49.9%-52.7%), 62.3% (60.5%-64.4%) to 43.0% (40.5%-45.5%), and 61.9% (61.3%-62.4%) to 36.7% (35.9%-37.6%) for the prevalent AF, new-onset AF, and no AF group, respectively (Figure 1). The five-year risk of HF hospitalisation went from 33.3% (32.1%-34.4%) to 30.3% (29.2%-31.4%) in the prevalent AF group, from 25.8% (24.2%-27.4%) to 29.6% (27.7%-31.5%) in the new-onset AF group, and from 28.4% (27.8%-28.9%) to 28.0% (27.2%-28.6%) in the no AF group. The five-year risk of stroke decreased from 8.5% (7.8%-9.1%) to 5.0% (4.4%-5.5%) in the prevalent AF group, 8.2% (7.2%-9.2%) to 4.6% (3.7%-5.5%) in the new-onset AF group, and 6.3% (6.1%-6.6%) to 4.9% (4.6%-5.3%) in the no AF group (Figure 2). Simultaneously, the proportion of patients prescribed anticoagulant therapy within 90 days after HF onset increased from 42.7% to 93.1% in patients with prevalent AF and 41.9% to 92.5% in patients with new-onset AF. Conclusion From 1997 to 2018, we observed an increase in patients with HF and coexisting AF. The five-year risk of mortality and stroke decreased across all patient groups regardless of AF-status. Additionally, prescriptions of anticoagulation therapy increased, and stroke risk in patients with HF and AF was reduced to similar levels as patients with HF without AF at the end of the study period.Figure 1 - Mortality in HF patientsFigure 2 - Stroke risk in HF patients

Left atrial volumetric-mechanical coupling index as a marker of subclinical primary heart involvement in systemic sclerosis

Abstract Background Primary heart involvement in systemic sclerosis (SSc) is a common yet often clinically silent marker of poor prognosis. Up to 80% of patients have histopathological evidence of heart involvement, highlighting the need for better screening and diagnostic methods. N-terminal pro-brain natriuretic peptide (NTproBNP), a well-established cardiac biomarker, is often increased in patients with SSc, but with a not fully understood mechanism. Meanwhile, left atrial volumetric-mechanical coupling index (LACI), a new echocardiographic parameter, has been shown to predict cardiovascular outcomes in heart failure patients and the general population, but it has not been studied in SSc. Purpose To identify new echocardiographic parameters, particularly related to left atrial volume and function, as markers of increased NTproBNP in SSc patients without overt heart involvement. Methods Consecutive SSc patients without overt heart disease referred for routine cardiac screening underwent 2D and 3D transthoracic echocardiography, including atrial and ventricular strain analysis. LACI was calculated by both 2D and 3D echocardiography as the ratio between the left atrial volume index and the tissue-Doppler-imaging septal a’ velocity. Patients with significant structural and functional changes suggestive of systolic or diastolic dysfunction or pulmonary hypertension, and those with impaired global left ventricular strain were excluded. Logistic regression, Pearson correlation coefficients, and area under the receiver-operating characteristic curve (AUC) are used to analyze the association and predictive power of LACI for elevated NTproBNP. Results A total of 36 SSc patients (55±10 years old; 34 (94%) women; mean disease duration 14±11 years) were included. Sixteen (44.4%) had diffuse cutaneous involvement (dcSSc). Seventeen (47%) patients had increased NTproBNP levels (i.e. &amp;gt;125 pg/mL). Among all tested variables, 3D LACI had the best correlation with NTproBNP values (r = 0.63, p&amp;lt;0.001). A 3D LACI of &amp;gt;2 associated with NTproBNP of &amp;gt;125 pg/mL (odds ratio 7.33 [95%CI 1.38-38.8]; p=0.01) and predicted these increased values with a sensitivity of 76.9% and a specificity of 81.2% (AUC 0.78). NTproBNP was also correlated with 2D LACI (r=0.55, p&amp;lt;0.001), peak left atrial longitudinal strain (r=-0.42, p=0.01), and left atrial contraction strain (r=0.48, p=0.005). Compared to patients with limited cutaneous involvement, those with dcSSc had higher NTproBNP values (250±139.6 vs 107.2±110.9 pg/mL, p=0.001), higher 3D LACI values (2.6±0.9 vs 1.9±0.5, p=0.02), with similar left atrial and ventricular strain parameters. Conclusion Left atrial volumetric-mechanical coupling index assessed by 3D echocardiography is significantly associated with and predictive of elevated NTproBNP levels in SSc patients without overt heart disease and may be a potentially useful non-invasive marker for screening for early subclinical heart involvement in SSc patients.

A larger reduction of spatial mean QRS-T angle during cardiac resynchronisation therapy is associated with a lower risk of mortality and heart failure hospitalisation

Abstract Background Predicting clinical outcome in heart failure patients undergoing cardiac resynchronization therapy (CRT) remains challenging, necessitating improved risk stratification for CRT recipients. Previous studies have shown an association between large spatial peak and mean QRS-T angles and cardiovascular disease. Little is known, however, about their relation to clinical outcome following CRT. Purpose To investigate the association between spatial peak and mean QRS-T angles and long-term clinical outcome following CRT initiation. Methods All patients with native LBBB receiving CRT at a large-volume tertiary care center between 2015 and 2020 were retrospectively evaluated. Spatial peak and mean QRS-T angles were derived from digital pre- and post-CRT 12-lead ECGs that were processed using Glasgow algorithm and Kors’ regression transformation. The QRS-T angles and their change after CRT were analyzed in relation to the primary composite endpoint of heart failure hospitalisation or all-cause mortality using Cox regression analysis adjusted for clinical covariates (age, gender, CRT-P or CRT-D, secondary ICD indication, ischemic etiology, NYHA class, LVEF, diabetes, atrial fibrillation, baseline QRS duration, NT-proBNP, and eGFR). Results The study group comprised 250 patients (a median age [Q1–Q3] of 72.2 years [64.5–76.3]; 22% female; 58% New York Heart Association (NYHA) class III-IV; LVEF 27% [22–30]) who were followed over a median follow-up time of 4.5 years [3.2–5.8] after CRT implantation. The median post-CRT spatial peak and mean QRS-angles were 142° [116–160] and 152° [127–166], and the median angle was decreased by 16° [-0.6–41] and 14° [-0.4–38], respectively. Both a larger post-CRT mean QRS-T angle (HR 1.20, 95%CI 1.08-1.33, p=&amp;lt;.001) and peak QRS-T angle (HR 1.08, 95%CI 1.01-1.17, p=0.046) were associated with the primary endpoint. A larger reduction of mean QRS-T angle, but not peak QRS-T angle, was associated with a risk reduction (HR 0.87, 95%CI 0.79-0.95, p&amp;lt;0.003). In Kaplan-Meier analysis, patients with a post-CRT mean QRS-T angle above median had a higher risk of reaching the endpoint (log-rank p=0.002, Figure 1). Conclusion Our results show that a larger magnitude of the post-CRT spatial peak and mean QRS-T angles, and a larger reduction of the latter, are associated with long-term heart failure hospitalisation and death. These findings suggest that spatial QRS-T angle may have a potential role in refined risk stratification of CRT patients.Figure 1.K-M curve spatial mean QRS-T

Clinical phenotypes in relation to outcomes in heart failure patients with cardiac resynchronization therapy and defibrillators (CRT-D): an unsupervised cluster analysis

Abstract Background Patients with heart failure undergoing CRT are an heterogenous and complex population. Selecting patients before implantation is essential to obtain a favorable response to CRT-D. Data-driven cluster analysis may be an approach to identify different patients’ phenotypic categories. Purpose To identify different clusters of patients with CRT-D who share similar clinical phenotypes, and to evaluate the associations between clusters and clinical outcomes, using cluster analysis. Methods Three agglomerative hierarchical cluster analysis were performed in CRT-D patients seen between 2010 and 2019 in French hospitals. Associations between clusters and death at one year and death during whole follow-up (FU) were evaluated using Cox regression analyses. Results The study included 23,029 CRT-D patients with no prior history of VT/VF/cardiac arrest (mean age 67.7 ± 9.9 years; 78.8 % male), who were analyzed in relation to 3 ways, as follows: the first group was a 50% random sample of all patients (n = 11,514), the second group included patients dead at 1 year (n = 1,604) and the third group included those alive at 3 years FU (n = 14,228). A cluster analysis was performed on each group. Four clusters were identified in the first group: Cluster 1 identified young patients with dilated cardiomyopathy and low prevalence of coronary artery disease (CAD), cardiovascular (CV) risk factors and comorbidities (chronic kidney disease, lung and liver disease) (low-risk phenotype); Cluster 2 was composed of male patients with CAD but low burden of CV risk factors and comorbidities (CAD phenotype); Cluster 3 included CRT recipients with several CV risk factors but low prevalence of comorbidities (CV risk factors phenotype); Cluster 4 identified old patients with high prevalence of CAD, atrial fibrillation, CV risk factors and comorbidities (clinical complex phenotype). These phenotypes were maintained in the other two groups (dead at 1 year and alive at 3 years FU), with the highest consistency for low-risk and high-risk phenotypes(Cluster 1 and 4 respectively). Compared with Cluster 1, Clusters 2, 3 and 4 were independently associated with an increased risk of all-cause death at 1-year FU and during the whole FU (Cluster 2: HR 1.21, 95% CI 1.08 - 1.36; Cluster 3: HR 1.15, 95%CI 1.04 - 1.26; and Cluster 4: HR 1.79, 95%CI 1.65 - 1.96). There were high prevalences of CAD, atrial fibrillation, mitral regurgitation, and comorbidities (which are all predictors of CRT-nonresponse) not only in Cluster 4 at baseline, but also among patients who died at 1-year FU in all 4 clusters. Conclusion Cluster analysis identified four statistically driven groups of CRT recipients, with specific clinical phenotypes and associated with different risks for all-cause death. Identifying those patients at higher risk of adverse events might help in the selection of patients with heart failure undergoing CRT-D implantation, especially in relation to CRT-nonresponse.Risk of all-cause death in 4 clusters

Effects of empagliflozin on myocardial transcriptome in rats with aortic stenosis-induced heart failure

Abstract Introduction Aortic stenosis (AS) represents one of the most prevalent valvular heart diseases and an important cause of heart failure. Currently, no medical therapies influence the natural history of aortic stenosis. Although sodium glucose co-transporter 2 inhibitors (SGLT2i) have improved cardiovascular outcomes in heart failure patients with both reduced and preserved ejection fraction, their action mechanisms are not clear. Transcriptome analysis present great potential to identify biomarkers of disease and to gain insight into disease pathophysiology. In this study, we analyzed myocardial mRNA profile in aortic stenosis rats treated with empagliflozin. Methods Eighteen weeks after supra-aortic banding surgery, male Wistar rats were divided into 3 groups: Sham (n=15); aortic stenosis (AS, n=27); AS+empagliflozin (AS-EMP, n=27). Empagliflozin (10 mg/kg/day) was added to rat chow for 8 weeks. Transcriptome of left ventricle (LV) myocardium was studied by RNA-sequencing (sample size: 5 per group). Differential gene expression was analyzed in R environment using the DESeq2 package. Genes were considered differentially expressed (DEG) when they exhibited a log2 fold change (log2FC) higher than 1 (upregulated) or lower than -1 (downregulated), coupled with an adjusted p-value below 0.05. Functional enrichment analysis using gene ontology was performed by the online tool Enrich. Statistical analysis: ANOVA and Tukey. Results AS-EMP had lower LV diastolic diameter (Sham 8.39±0.57; AS 9.80±0.53*; AS-EMP 9.08±0.87# mm; p&amp;lt;0.05: * vs Sham; # vs AS), left atrium diameter (Sham 5.68±0.40; AS 9.67±1.00*; AS-EMP 8.97±1.36*# mm; p&amp;lt;0.05: * vs Sham; # vs AS), and LV mass (Sham 0.85±0.11; AS 2.19±0.27*; AS-EMP 1.76±0.34*# g; p&amp;lt;0.05: * vs Sham; # vs AS) than AS. A total of 1246 differentially expressed genes were identified, comprising 663 upregulated genes (70 genes in AS vs SHAM; 593 in AS-EMP vs AS) and 583 downregulated genes (35 genes in AS vs SHAM; 548 in AS-EMP vs AS). Most of the differentially expressed genes were enriched in processes such as extracellular matrix and structure organization, signal transduction regulation, and substrate-dependent cell migration (AS vs SHAM), as well as myocardial contraction, negative regulation of programmed cell death, and mitochondrial membrane organization (AS-EMP vs AS). The main upregulated genes were Loxl1, Mfap4, Postn, Col8a1, Pi16, and Nppa in AS vs SHAM; and Mxra8, Zfta, Pnisr, Thoc1, and Ralbp1 in AS-EMP vs AS comparison. The main downregulated genes were Mxra8, Ralbp1, and Tubgcp6 in AS vs SHAM; and Itgb5, Ltbp2, Tmem109, Plec, and Rorc in AS-EMP vs AS comparison. Conclusion We identified myocardial genes and biological processes that are potentially involved in aortic stenosis-induced heart failure. Empagliflozin attenuates cardiac remodeling and modulates myocardial genes involved with myocyte contraction, apoptosis, and mitochondrial organization in aortic stenosis rats.

Neurodegeneration is highly associated with comorbidity burden in HFrEF patients

Abstract Background Heart failure (HF) is associated with cognitive decline and risk for dementia. Blood levels of amyloid beta 40 and 42 (Aβ40, Aβ42), tau protein (tau), and neurofilament light chain (NfL) have been found to be altered in neurodegenerative disease. Previous research has established a clear association between these neuromarkers and the risk of developing cognitive dysfunction and mortality in the general population. Objective The aim of this study was to investigate the association between the respective neuromarkers and comorbidity burden, as well as to explore whether comorbidity burden impacts the relationship between neuromarkers and outcome in HF patients. Methods Plasma levels of Aβ40, Aβ42, tau, and NfL were quantified using a single-molecule array assay. The primary outcome parameter was all-cause mortality. Results A total of 470 HFrEF patients were enrolled in the study, with a median age of 62 years (IQR: 52–72); 77% were male. Median NT-proBNP concentration was 1812 pg/ml (IQR: 718–3881). Elevated levels of all biomarkers were closely associated with comorbidity burden (Figure 1). All neuromarkers showed increased levels in individuals with chronic kidney disease (CKD) and known carotid artery stenosis (CAS), except for Aβ40, which did not show significant elevation in CAS (NfL: p&amp;lt;0.001 for both; t-tau: p&amp;lt;0.001 and p=0.041; Aβ40: p&amp;lt;0.001 and p=0.050; Aβ42: p&amp;lt;0.001 and p=0.033, respectively). In patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), only NfL levels were significantly elevated (p&amp;lt;0.001 for both), whereas atrial fibrillation (AF) was associated with higher levels of NfL and t-tau (p&amp;lt;0.001 for both). In individuals with iron deficiency, only Aβ42 levels were significantly higher (p=0.025). All biomarkers showed significant associations with all-cause mortality [crude HR for an increase in 1-log unit (95%CI): NfL 4.44 (3.02-6.53), t-tau 5.04 (2.97-8.58), Aβ40 3.90 (2.27-6.72), Aβ42 5.14 (2.84-9.32); p&amp;lt;0.001 for all] (Figure 2). These associations remained statistically significant after adjusting for comorbidity burden including AF, T2DM, CAD, CKD, CAS and ID [adjusted HR for an increase in 1-log unit (95%CI): NfL 3.28 (1.93-5.57), t-tau 3.96 (2.07-7.57), Aβ40 2.42 (1.34-4.38), Aβ42 3.05 (1.56-5.97); p&amp;lt;0.01 for all]. Conclusion The findings suggest a close connection between elevated levels of markers of neurodegeneration and increased comorbidity burden in HFrEF patients. While this association may indicate the cumulative risk leading to neuronal injury and HFrEF progression, a causal relationship cannot be excluded. The observed accelerated neurodegeneration in HFrEF underscores the need for further investigation into this complex interplay.Figure 1Figure 2

The effects of angiotensin receptor-neprilysin inhibitors on clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: real-world evidence from the CCA Database-HF Center

Abstract Background Recent clinical trials have demonstrated the potential efficacy and safety of angiotensin receptor-neprilysin inhibitors (ARNI) in patients with heart failure (HF) with mildly reduced or preserved ejection fraction. Nevertheless, the generalizability of these findings in real-world clinical settings remains to be determined. We aimed to compare the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB)on clinical outcomes in HF patients with mildly reduced or preserved ejection fraction. Methods Patient-level data was derived from the China Cardiovascular Association Database-HF Center Registry. We included exclusively a subpopulation of HF patients with left ventricular ejection fraction (LVEF) &amp;gt;40% and comorbid with hypertension. Patients prescripted with ARNI at discharge and sustaining to ARNI therapy during follow-up were categorized as the ARNI group, while those maintaining the usage of ACEI/ARB after discharge were designated as the ACEI/ARB group. In complete cases, the primary endpoint of all-cause mortality at one year was assessed by the 1:1 propensity score matching (PSM) method. Results In all HF patients with LVEF &amp;gt;40% comorbid with hypertension, the usage of ARNI has increased from 0.9% in 2017 to 37.2% in 2021. A total of 3348 patients in the ARNI group and 7688 patients in the ACEI/ARB group were identified for comparative effectiveness. After 1:1 PSM, 5482 patients were included in the primary analysis, with 2741 patients in each treatment arm. The proportion of patients receiving higher dosages of ARNI (200mg/d and 400mg/d) was 20.9%, 26.6%, 29.2%, and 30.3% at discharge, 1-month, 3-month, and 1-year, respectively. Over the 1-year follow-up, ARNI was associated with a 20% relative reduction in all-cause death compared to the ACEI/ARB therapy (10.5% vs. 12.9%, adjusted hazard ratio [HR], 0.80 [95% CI, 0.69-0.94], P=0.005). The absolute risk difference in all-cause death between ARNI and ACEI/ARB arms was 2.88 per 100 patient-years (incidence rate difference, -2.88 [95% CI, -4.86 to -0.9]). Cardiovascular death also tended to decrease in the ARNI group but with missed statistical significance (4.5% vs. 4.9%, adjusted HR, 0.89 [95% CI, 0.70-1.14], P=0.373). Treatment benefits were more significant in those with LVEF between 40-50% (adjusted HR, 0.62 [95% CI, 0.48-0.79]), 50-60% (adjusted HR, 0.85 [95% CI, 0.68-1.06]), but not observed in HF patients with LVEF&amp;gt;60% (adjusted HR, 1.80 [95% CI, 1.08-2.98]; Pinteraction&amp;lt;0.001). Conclusion In real-world clinical settings, treatment with ARNI was associated with a significant relative risk reduction in all-cause mortality compared with ACEI/ARB in HF patients with mildly reduced or preserved LVEF. The cardiovascular benefit was concentrated in patients with LVEF ≤60%.

Prognostic impact of mitral valve geometry in patients with secondary mitral regurgitation: a secondary analysis of the MITRA-FR trial

Abstract Background Mitral valve (MV) transcatheter edge-to-edge repair (TEER) has emerged as a second line therapy on top of guidelines-directed medical treatment (GDMT) in heart failure (HF) patients with severe secondary mitral regurgitation (SMR). Following the disparate results of the COAPT and MITRA-FR pivotal trials, echocardiographic markers of LV remodeling and MR severity have been proposed to select patients most likely to benefit from MV-TEER. The characterization of MV geometry arises as a potential tool to stratify risk of outcomes in SMR patients, who underwent classical surgery or MV-TEER intervention. However, it remains unknown whether MV geometry parameters were associated with prognosis in MITRA-FR patients and whether MV-TEER could modulate their impact on outcomes. Purpose To evaluate the association between MV geometry and outcomes of HF patients with SMR in the MITRA-FR trial, as well as the impact of SMR treatment modality. Methods Thirteen MV geometry parameters were assessed from baseline transthoracic echocardiograms in patients from the MITRA-FR trial. The prognostic impact of MV geometry parameters was studied on top of the baseline clinical variables used in the primary analysis of MITRA-FR (i.e. age, atrial fibrillation [AF], ischemic cardiomyopathy, myocardial infarction, left ventricular ejection fraction [LVEF] and effective regurgitant orifice area [EROA]). The primary endpoint was the composite of all-cause mortality or HF hospitalization (HFH) within 2 years. The effect of treatment arms (MV-TEER plus GDMT vs. GDMT alone) on this association was also evaluated. Results Among the 307 patients included in the pivotal trial, 272 were analyzed in the present study (i.e. 135 from the GDMT group and 137 from the GDMT + MV-TEER group). Mean age was 70±10, 74% male. 50% had ischemic cardiomyopathy and 34% AF. LVEF was 33±7% and EROA was 31±11 mm². MV geometry parameters were presented for the whole population and according to the randomization group in the Table. Among these parameters, only MV tenting area remained independently associated with the primary endpoint (Hazard Ratio (HR) = 1.22 per 1 cm², Confidence Interval (CI) = 1.01-1.47; p=0.041) after multivariate analysis (Figure). Tenting height was independently associated with the risk of HFH (HR=1.07 per 1 mm, CI=1.00-1.14, p=0.037), but no MV geometry variable was associated with all-cause death. These findings remained consistent in both treatment arms (p&amp;gt;0.20 for interaction). Conclusion In HF patients with SMR included in the MITRA-FR trial, MV tenting area and MV tenting height were independently associated with the risk of HFH or all-cause mortality and HFH respectively, without any difference according to treatment arms. These data suggest that MV tethering provides an incremental prognostic value beyond classical echocardiographic variables, including EROA, and then should be considered in the risk stratification of patients with HF and SMR.Table of MV geometry parameters featuresMultivariate analysis (Forrest-plots)

Explainable machine learning and multi-modal data for predicting readmission in patients with heart failure

Abstract Background Cardiovascular diseases (CVDs) are among the leading causes of mortality and morbidity globally, with an estimated 1 million hospital admissions for CVD in England in 2019/20, leading to 5.5 million bed days. In addition, patients with CVDs have a notably high rate of hospital readmission, with approximately one in four patients experiencing heart failure (HF) being readmitted within one month of discharge. We explored whether machine learning models trained on electrocardiogram (ECG) and patient electronic health records (EHRs) can support decision-making and risk management and ultimately improve health outcomes for HF patients. Purpose The project aims to develop a machine learning model to predict health outcomes for HF patients. To test the hypothesis, we trained and tested an explainable machine learning model to predict the risk of mortality and hospital readmission rate for HF patients. Methods We used EHR data and tabulated ECG records to train an XGBoost model to predict the risk of 30-day mortality and 30-day hospital readmission for HF patients. EHR data from a cohort of 2,868 patients with their ECG records were used for model development. We extracted a total of 78 features from the ECG data, such as heart rate variability (HRV), P-wave durations, and QT intervals. These ECG features were combined with coded and free-text EHR data (e.g., demographic information, diagnosis, medication history, and lab results) and used as tabular inputs to the XGBoost model. Of the 2,868 patients, an internal set of 574 patients stratified by age, sex, and health outcomes (30-day mortality and 30-day hospital readmission) were held out for testing. Results Among 2,868 HF patients with 10-year follow-up, 1065 patients were reported for mortality or hospital readmission within 30 days of discharge. When the machine learning model was trained on ECG data in addition to EHR data, the model was able to predict patient mortality and hospital readmission rate in the test set with an area under the curve (AUC) of 0.91 and 0.70, respectively. For mortality prediction, the model achieved a sensitivity and specificity of 0.81 and 0.82, respectively, when employing an operating point with minimum difference between the sensitivity and specificity. When the threshold was adjusted to favor sensitivity at 0.91, the model specificity decreased to 0.74. The machine learning model also identified high sensitive troponin levels, QT dispersion, and lactate dehydrogenase levels as features of high importance for predicting the outcomes for HF patients. Conclusions Our developed machine learning model was able to predict mortality and readmission risks in HF patients using multi-modal data. Upon further validation, the machine learning model has the potential to be tested for supporting clinical decision-making and risk management for HF patients.ROC CurveFeature Importance

Time taken for cardiology care and one-year results for primary care physicians' referrals for cardiology consultation in heart failure patients: clinical implications for heart failure management

Abstract Background and Purpose The clinical trajectory of patients with heart failure (HF) is characterised by frequent episodes of decompensation requiring urgent medical assistance, hospitalisations, and an increased risk of mortality. HF clinical guidelines recommend early visits by health professionals after hospital discharge, yet little evidence exists regarding the associations between delayed medical attention and outcomes in HF patients. To assess the clinical impact of the time taken to receive cardiology care for referrals from primary care physicians (PCPs) to a cardiology department in HF patients, we selected 6,859 HF patients who visited the cardiology service at least once between 2010 and 2021. Methods Using an interrupted time series regression model, we analysed the impact of integrating e-consultations into the healthcare model (implemented in 2013) and evaluated the time taken to receive cardiology care, as well as all-cause, cardiovascular (CV), and HF-related hospital admissions and mortality. The primary objective of this analysis was to examine the associations between delays in cardiology care following a PCP referral and 1-year outcomes (HF-related, cardiovascular, and total hospitalisations; and HF-related, cardiovascular, and total mortality). Results Almost 50% were women, and the mean age was 77.8 years. Arterial hypertension (79.6%), diabetes (34%), atrial fibrillation (51.4%), ischemic heart disease (20.4%), and cerebrovascular disease were the most prevalent comorbidities. The mean time from PCP referral to cardiology consultation in the overall population was 22.3 days: &amp;lt;8 days in 53.9%, 8-14 days in 17.1%, 15-30 days in 15.9%, and &amp;gt;30 days in 13.0% of patients, respectively. One year after cardiology consultation, 68.6% of patients required assistance in an Emergency Department; 22.5% were hospitalised for any cause, 14.9% for cardiovascular reasons, and 9.2% for HF-related issues. Moreover, total mortality at 1-year was 8.6%, comprising 4.3% cardiovascular mortality and 1.3% HF-related deaths. Multivariate analysis of the relationship between the time taken to receive cardiology care and 1-year outcomes revealed a significant increased risk associated with a longer delay in cardiology assistance, particularly evident in the subgroup of patients with previous hospital admissions due to worsening HF (see Table). Conclusions Throughout the follow-up period, a reduced time taken to receive care was independently associated with better 1-year outcomes. We believe that our experience can contribute to the development of a more efficient ambulatory care pathway for HF patients, especially those at high risk, such as those with a history of hospitalisation due to worsening events. Our findings further support the clinical guideline recommendation for early contact by health professionals following hospital discharge, extending it to include PCP referrals for cardiology consultations.

Frailty and MECKI score in predicting mortality in advanced heart failure

Abstract Background Physical frailty (PF), characterized by decreased physiological reserves and increased vulnerability to stressors, has emerged as a significant predictor of adverse outcomes in heart failure (HF). The MECKI (Metabolic Exercise Cardiac Kidney Index) score, a composite index derived from cardiopulmonary exercise testing parameters and renal function, has shown promise in predicting outcomes in HF patients. Purpose The aim of the study is to evaluate the independent prognostic role of the MECKI score and PF on mortality in patients with advanced heart failure (AHF). Methods Ninety-one patients with AHF were enrolled, including 42 on the heart transplant waiting list, 10 undergoing evaluation for listing, and 49 removed from the list due to transplant contraindications or reaching age limits. All patients included in the study were on medically optimized therapy. MECKI score assessment was conducted upon enrollment, along with hematological and biochemical evaluations including creatinine, hemoglobin, Na+, and NT-pro-BNP levels. Patients also underwent echocardiography assessing ejection fraction (EF), TAPSE, Inferior Vena Cava (IVC) diameters, and PASP. Additionally, all patients performed the 6-minute walk test (6MWT) and cardiopulmonary exercise testing with assessment of VO2max and VE/VCO2. Frailty was assessed based on modified Fried criteria. Results The mean age was 56.5±11.2 years. Mean NYHA class was 2.7±0.6, EF was 28.8±7.6, TAPSE was 17.5±4.2, and NT-proBNP was 2912.2±3249.0. Mean VO2max was 12.0±3.5 ml/kg/min, and mean distance walked during 6MWT was 278.8±137.2 meters. Mean frailty score was 3.2±1.2 while mean MECKI score was 15.2±14,2. During a mean follow-up of 32.0±15.3 months, there were 21 deaths, 15 patients received heart transplants, and 1 patient underwent LVAD implantation. Stratified data for mortality showed statistically significant differences in deceased patients compared to survivors regarding NYHA class (3.2±0.3 vs 2.6±0.7; p&amp;lt;0.001), Frailty Index (4.4±0.7 vs 2.7±1.13; p&amp;lt;0.001), NT-proBNP (5425.0±2863.0 vs 1731.0±1618.0; p&amp;lt;0.001), VE/VCO2 (42.7±12.3 vs 35.0±9.1; p&amp;lt;0.003), and MECKI score (29.4±15.2 vs 11.2±11.2; p&amp;lt;0.001). Linear regression analysis demonstrated a significant positive correlation for Frailty Index and MECKI score with age, NYHA class, VE/VCO2, IVC, and NT-proBNP, while showing a negative correlation with TAPSE, VO2max, and 6-minute walk test. Cox regression analysis on mortality demonstrated the predictive role of Frailty (HR=2.121; 95%CI=1.017-4.421; p=0.045) and MECKI score (HR=1.043; 95%CI=1.009-1.079; p=0.014) independently from age, sex, NYHA class, NT-proBNP, EF, TAPSE, VO2max, 6MWT, and IVC diameter. ROC curves demonstrated an AUC of 0.896 for MECKI score and mortality, and 0.884 for Frailty Index and mortality. Conclusions The MECKI score and physical frailty are both valid independent predictors of mortality in patients with advanced heart failure.

Clinical correlates and prognostic impact of cognitive decline in patients with heart failure and preserved ejection fraction: insights from PARAGON-HF

Abstract Background Cognitive decline is common in patients with heart failure (HF), but its clinical correlates and prognostic impact are not well understood in this population. Purpose To examine the baseline variables associated with cognitive decline and the associations between cognitive decline and HF outcomes in patients with heart failure and preserved ejection fraction (HFpEF). Methods We analyzed cognitive function, as measured by the Mini-Mental State Examination (MMSE), in 2895 patients with HFpEF enrolled in a pre-specified sub-study of PARAGON-HF. Logistic regression analysis was performed to determine the factors associated with cognitive decline i.e., a decrease in MMSE score of ≥3 points by 48 weeks. Time-updated Cox proportional hazards regressions and semiparametric proportional rates models were used to examine the subsequent risk of clinical outcomes after a decline in MMSE scores of ≥1-, 2- and 3-points during follow-up respectively, adjusted for known prognostic variables including NT-proBNP and baseline MMSE. Results A total of 450 (15.5% of the population) patients experienced a decrease in MMSE score of ≥3 points from baseline, at any follow-up visit. The corresponding number for a decrease in MMSE score of ≥2 points and ≥1 point was 755 (26.1%) and 1231 (42.5%), respectively. Independent predictors of cognitive decline at 48 weeks included older age, living in Latin America or the Asia/Pacific region, ischemic etiology, prior HF hospitalization, history of stroke/TIA, and lower serum albumin level (Figure 1). There was a graded relationship between the size of the decrease in MMSE score from baseline and the subsequent risk of mortality. Notably, a decrease of ≥3 points was associated with a 50% increase in the subsequent risk of death from any cause (adjusted HR 1.53, 95% CI 1.10-2.11) and a 90% elevation in risk of death from cardiovascular causes (1.89, 1.25-2.86), respectively, after extensive adjustment for known prognostic variables and baseline MMSE score. By contrast, cognitive decline during follow-up was not associated with a higher risk of HF hospitalization or the composite of HF hospitalization or CV death (Figure 2). Conclusions In patients with HFpEF, a decline in MMSE score during follow-up is independently associated with a graded increase in the risk for mortality, but not of HF hospitalization.The predictors for cognitive declineRisk of outcomes after a decline in MMSE

Association between echocardiographic parameters and abnormal spirometry among chronic heart failure patients

Abstract Background A significant proportion (10-40%) of heart failure (HF) patients have concomitant pulmonary disease which have negative effects on cardiovascular outcome of patients. Because of the similarities in symptoms between HF and pulmonary disease, the prevalence of concomitant pulmonary disease may be underestimated. Early detection manage accordingly may improve outcomes of HF patients. We aimed to study clinical and echocardiographic parameters identifying HF patients with concomitant pulmonary disease. Methods This cross-sectional study included adults (age≥18 years) who were diagnosed with HF. The echocardiogram, arterial blood gas and pulmonary function test (PFT) were performed. The patients were classified into normal and abnormal (obstructive and restrictive) PFT patterns. The primary outcome was the association between echocardiographic parameters and abnormal PFT. The receiver operating characteristic (ROC) curve was performed to evaluate diagnostic performance of echocardiographic parameter in detecting abnormal PFT. Results A total of 57 patients was enrolled, of which 32 patients (56.14%) had normal PFT, 14 patients (24.56%) had obstructive PFT, and 11 patients (19.30%) had restrictive PFT. The clinical characteristics were not different between groups. ROC curve demonstrated that only left atrial volume index (LAVI) and main pulmonary artery (MPA) diameter had significant diagnostic accuracy to predict abnormal PFT with AUC of 0.72 (95%CI 0.57-0.87) and 0.66 (95%CI 0.51-0.80) respectively. Using combination of LAVI (cutoff 40mm2/m2) and MPA diameter (cutoff 22.0 mm) had a sensitivity of 95.7% (95%CI 78.05-99.89%) and specificity of 41.94% (95%CI 24.55-60.92%) in detection patients with abnormal PFT. Conclusion Almost half of HF had concomitant abnormal PFT. The combination of LAVI and MPA diameter can identify patients with abnormal PFT with high negative predictive value and should be considered as screening parameters in HF patients.