Heart Failure Cohort Research Articles

Amino acid profiling to predict prognosis in patients with heart failure: an expert review.

Heart failure is a complex disease with a poor prognosis. A number of widely used prognostic tools have limitations, so efforts to identify novel predictive markers and measures are important. As a metabolomics tool, amino acid profiling has shown promise in predicting heart failure prognosis; however, the evidence has not yet been sufficiently evaluated. We describe the utilization of amino acids in the healthy heart and in heart failure before reviewing the literature on amino acid profiling for prognostic prediction. We expertly interpret the findings and provide suggestions for future research to advance the understanding of the prognostic potential of amino acid profiling in heart failure. Our analysis revealed correlations between amino acid biomarkers and traditional prognostic factors, the additional prognostic value of amino acid biomarkers over traditional prognostic factors, and the successful use of amino acid biomarkers to distinguish heart failure aetiology. Although certain amino acid biomarkers have demonstrated additional prognostic value over traditional measures, such as New York Heart Association functional class, these measures are deeply rooted in clinical practice; thus, amino acid biomarkers may be best placed as additional prognostic tools to improve current risk stratification rather than as surrogate tools. Once the metabolic profiles of different heart failure aetiologies have been clearly delineated, the amino acid biomarkers with the most value in prognostic prediction should be determined. Amino acid profiling could be useful to evaluate the pathophysiology and metabolic status of different heart failure cohorts, distinguish heart failure aetiologies, and improve risk stratification and prognostic prediction.

Spironolactone Utilization among Patients with Reduced and Preserved Ejection Fraction Heart Failure

Background: Spironolactone is a mineralocorticoid receptor antagonist indicated for the management of heart failure with reduced ejection fraction (HFrEF). In a previous clinical trial, spironolactone significantly lowered the incidence of heart failure (HF) hospitalizations among HF patients with preserved ejection fraction (HFpEF). Real world utilization of spironolactone in HFrEF and HFpEF is unknown. Methods: We conducted a retrospective cohort study using data from FDA’s Sentinel System. We identified patients with HFrEF or HFpEF using diagnosis and procedure codes from a previously validated algorithm. We required patients to be continuously enrolled in the 183 days prior to HF diagnosis. Follow-up started on the day of HF diagnosis and ended at the earliest occurrence of a spironolactone dispensing, disenrollment, death, or end of data. We calculated the proportion of spironolactone utilization, and for those initiating treatment, we estimated the dose and duration of the first continuous treatment episode. Results: Among 2,009,529 HFrEF patients, 57.8% were male, and mean age was 73.8 ± 12.1 years. Among 9,257,514 HFpEF patients, 42.7% were male, and mean age was 73.0 ± 12.1 years. The proportion of spironolactone utilization following HFrEF diagnosis was 20.7% versus 7.6% after HFpEF. The median time (days) to initiation of spironolactone after HFrEF diagnosis was 90 (IQR: 19–385) versus 286 (IQR: 57–851) after HFpEF diagnosis. The median duration (days) of first treatment episode in HFrEF patients was 120 (IQR: 44–321) and 114 (IQR: 32–301) for HFpEF patients. The median dose was similar (25 mg/day) for both HF cohorts. Conclusion: Findings of low real-world utilization of spironolactone from our large, geographically, and demographically diverse multi-site study in the US are consistent with reports from smaller studies in the literature. Similar spironolactone dosing and duration were observed in both the HFpEF and HFrEF cohorts. Future research characterizing spironolactone treated and untreated HFpEF cohorts will be needed to identify treatment gaps.

Real-world eligibility for vericiguat according to trial, guideline, and labelling eligibility criteria: data from the Swedish Heart Failure Registry

Abstract Introduction The VICTORIA trial demonstrated the efficacy and safety of vericiguat in patients with worsening heart failure (HF) and an ejection fraction (EF) of <45%. Trial selection criteria might limit the external validity, and the perceived low generalisability may be an underlying reason for poor implementation of new treatments. Purpose We calculated the proportions of patients who would be eligible for vericiguat according to trial, guideline, and labelling scenarios in a large and unselected real-word HF population, and compared eligible to ineligible populations for patient characteristics and outcomes. Methods From the Swedish HF Registry (SwedeHF), 41,635 patients with EF<40% recorded between May 2000 and December 2018 were considered. We applied the VICTORIA trial's selection criteria, the 2021 European Society of Cardiology (ESC) guidelines' recommendation, and the regulatory labelling of vericiguat according to the Food and Drug Administration and European Medicines Agency. Outcome rates (cardiovascular [CV] and non-CV death, and first HF hospitalisation [HFH]) were compared between eligible and ineligible patients using exact Poisson test with a significance level of 5%. We also analysed 60,351 patients with EF<50% for the trial scenario. Results Eligibility for vericiguat based on the trial, guideline, and labelling criteria were 21.2%, 25.7%, and 44.5%, respectively (Figure 1). The criteria with major impacts on eligibility were: 1) in the trial scenario - inclusion criteria: recent HFH (within 6 months) and elevated NT-proBNP (met by 47.5% and 74.4% of the population, respectively), exclusion criteria - nitrate use (14.0%); 2) in the guideline scenario: recent HFH and HF duration longer than 6 months (as a proxy for optimal medical therapy) (47.5% and 57.6%, respectively); 3) in the labelling scenario: recent HFH (47.5%). In patients with EF<50%, trial eligibility was slightly lower, and the impact of selection criteria was overall similar to those with EF<40%. Overall, eligible patients were older, less likely to be female, had more severe HF and comorbidities, and had greater mortality and morbidity (Figure 1). Conclusion In a large and contemporary real-world cohort of HF with EF<40%, eligibility for vericiguat according to the trial and guideline scenarios was limited, i.e. ∼20–25%, whereas it was higher according to the labelling scenario, i.e. ∼45%. The VICTORIA trial's selection criteria successfully selected a HF population enriched for CV events but also with a higher risk of non-CV events, which is consistent with more severe HF and comorbidities in eligible vs. ineligible patients, but the requirement for recent worsening HF also rendered many patients ineligible. Our findings might provide insights for designing more inclusive and feasible future trials and might help stakeholders assess the consequences of future trial eligibility. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bayer AG

Cerebral saturation is associated with physical activity and post-discharge mortality in heart failure patients

Abstract Background The cross-sectional relationship between heart failure (HF) and cerebral oxygenation has been studied in the past but the prognostic significance of this relationship has been limited. Here, we aimed to assess the role of cerebral tissue oxygen saturation (SctO2) as a risk factor for HF mortality and rehospitalization as well as evaluate the association between SctO2 with physical activity in a Swedish prospective HF cohort. Methods Ninety-five patients hospitalized for HF (mean age 70 years; 21% women) were examined with near-infrared spectroscopy (NIRS) and screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 1377 (interquartile range, 245–2392) and 293 (14–2363) days, respectively. Associations between SctO2 at rest, post-discharge mortality and re-hospitalization were analyzed using multivariable Cox regression analysis adjusted for age, sex, body-mass index, smoking, prevalence of atrial fibrillation, prevalence of diabetes and systolic blood pressure. The associations between SctO2 and self-reported physical activity were explored by using logistic regression analysis adjusted for the aforementioned risk factors. Results A total of 25 patients (26%) reported to be engaged in physical activity less than one hour throughout the week. In the fully adjusted Cox regression model, low SctO2 at rest was associated with post-discharge mortality (HR, 0.77; CI, 0.66–0.91; p=0.002). However, low SctO2 was not associated with post-discharge rehospitalization risk (HR, 0.94; CI, 0.88–1.01; p=0.092). In the fully adjusted logistic regression models, low SctO2 at rest was associated with decreased physical activity (<1h per week), (OR 1.22; CI, 1.05–1.42; p=0.01). Conclusion We have demonstrated that low cerebral tissue oxygen saturation at rest is associated with post-discharge mortality in patients hospitalized for HF, independently of traditional risk factors. In addition, low cerebral tissue oxygen saturation at rest is associated with low physical activity. These findings highlight the role of cerebral saturation as a risk factor for cardiovascular prognosis, as well as underline the potential importance of taking cerebral perfusion into account when treating for heart failure. Funding Acknowledgement Type of funding sources: None.

Incidence of heart failure and renal endpoints in heart failure patients with and without severe chronic kidney disease: a nationwide real-life study of 21,959 patients

Abstract Background Renal endpoints like end stage renal disease (ESRD) and a 50% decline in estimated glomerular filtration rate (eGFR) have been used in recent randomized clinical trials in heart failure (HF). However, the distribution of these events in larger real-life HF cohorts is unknown Purpose We examined the risk of traditional HF endpoints like death and worsening HF and the risk of these new renal endpoints in HF with and without severe chronic kidney disease (+/−eGFR 30 ml/min/1.73 m2) at the time of diagnosis of HF. Methods From nationwide registries, we identified patients receiving a diagnosis of HF from 2014–2018. Patients were included if they had creatinine available in proximity of the diagnosis (90 days before inclusion). Outcomes comprised of: (i) all-cause mortality, (ii) HF worsening, (iii) end stage renal disease and (iv) sustained 50% eGFR decline. 4-year rates of the primary outcomes were estimated using cumulative incidence function adjusted for competing risk of death, and multivariable Cox proportional hazards models were used to examine the association of covariates with a combined endpoint of the primary outcomes. Results We included 21,959 patients with HF and known CKD status. Median age was 73.9 years, and 7% had an eGFR <30 mL/min/1.73 m2. There were few differences in baseline characteristics for patients with and without eGFR below 30. Patients with eGFR below 30 were elder and had more comorbidities. The mortality rate was 33.9% for patients with eGFR≥30 and 70.4% for patients with eGFR <30. For patients with eGFR <30 at the time of HF diagnosis renal outcomes were more pronounced as the first event as compared to patients with eGFR ≥30. The risk of all-cause mortality and HF hospitalization as first event was comparable between eGFR ≥30 and eGFR<30 (22.7% vs 22.5% and 25.8% vs 22.5%, respectively). The risk of end-stage renal disease as first event was significantly higher for patients with eGFR <30 (0.03% vs. 33.8%). The risk of a sustained 50% decline in eGFR was 4.6% for patients with eGFR ≥30 and 1.0% for patients with eGFR<30 (figure 1). Across all important subgroups an eGFR <30 ml/min/1.73 m2 was associated with an increased rate of the composite endpoint of death, worsening HF or a renal endpoint, and no interactions were observed (P>0.01 for all) (figure 2). Conclusion The risks of newly introduced renal trial-endpoints in a large real-life cohort of HF patients was low compared to the risks of death or worsening HF if eGFR ≥30 ml/min/1.73 m2 at the time of diagnosis of HF. However, this pattern changed in HF patients with a eGFR <30 ml/min/1.73 m2 at the time of diagnosis time of HF. The present study provides important insights into cardiorenal epidemiology in HF and have implications for planning of future trials. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Herlev/Gentofte Hospital

Impact of Worsening Heart Failure on Long-Term Prognosis in Patients With Heart Failure With Reduced Ejection Fraction

Worsening heart failure (HF), defined as hospitalization for worsening signs and symptoms of HF or the need for urgent intravenous diuretics, is often considered a surrogate of poor prognosis in clinical trials. However, data on the prognostic implications of worsening HF in patients with HF and reduced ejection fraction is limited. Patients who had a first echocardiographic diagnosis of left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) ≤45%, were identified. Worsening HF was defined as hospitalization for HF or urgent need for intravenous diuretics. All-cause mortality was chosen as the study end point. A total of 1,801 patients (mean age 64 ± 12years, 74% men) were analyzed. Worsening HF was observed in 275 patients (15%) during a median follow-up of 20months, while, 435 patients (24%) died during a median follow-up of 60months (Interquartile range 28 to 60months). The 5-year survival rate was significantly lower in the worsening HF cohort compared with the non-worsening HF cohort (Log-rank p <0.0001), and it was significantly different between the worsening HF cohort and the nonworsening HF cohort for LVEF ≤25% (log-rank p <0.0001) and LVEF 26% to 34% (log-rank p=0.038) but not for LVEF 35% to 45% (log-rank p=0.14). After adjustment for important clinical and echocardiographic predictors, worsening HF was independently associated with a higher risk of all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.09 to 1.96, p=0.011). In conclusion, worsening HF, defined by HF hospitalization or the urgent need for intravenous diuretics, is independently associated with poor long-term prognosis in patients with HF and reduced ejection fraction.

Deep learning of ECG waveforms for diagnosis of heart failure with a reduced left ventricular ejection fraction

The performance and clinical implications of the deep learning aided algorithm using electrocardiogram of heart failure (HF) with reduced ejection fraction (DeepECG-HFrEF) were evaluated in patients with acute HF. The DeepECG-HFrEF algorithm was trained to identify left ventricular systolic dysfunction (LVSD), defined by an ejection fraction (EF) < 40%. Symptomatic HF patients admitted at Seoul National University Hospital between 2011 and 2014 were included. The performance of DeepECG-HFrEF was determined using the area under the receiver operating characteristic curve (AUC) values. The 5-year mortality according to DeepECG-HFrEF results was analyzed using the Kaplan–Meier method. A total of 690 patients contributing 18,449 ECGs were included with final 1291 ECGs eligible for the study (mean age 67.8 ± 14.4 years; men, 56%). HFrEF (+) identified an EF < 40% and HFrEF (−) identified EF ≥ 40%. The AUC value was 0.844 for identifying HFrEF among patients with acute symptomatic HF. Those classified as HFrEF (+) showed lower survival rates than HFrEF (−) (log-rank p < 0.001). The DeepECG-HFrEF algorithm can discriminate HFrEF in a real-world HF cohort with acceptable performance. HFrEF (+) was associated with higher mortality rates. The DeepECG-HFrEF algorithm may help in identification of LVSD and of patients at risk of worse survival in resource-limited settings.

Incidence, severity, risk factors and outcomes of acute kidney injury in older adults: systematic review and meta-analysis.

Old age was identified as a strong risk factor for acute kidney injury (AKI). Our objectives were to provide estimates of AKI, risk factors and outcomes in patients ≥ 75years for whom data are scarce. Observational studies and randomized controlled trials between 2005 and 2021 with patients of mean or median age ≥ 75years, reporting AKI according to current definitions. Data on AKI incidence, risk factors and mortality were analyzed separately in unselected (UC) and acute heart failure (AHF) cohorts. Twenty-six observational studies and 4 randomized controlled trials with 51,111 UC and 25,414 AHF patients were included. Ages averaged 79.4 and 79.8years, respectively. Pooled risk ratios (RRs) of AKI rates were 26.29% (95% confidence intervals (CI) 13.20-41.97) (UC) and 24.21% (95% CI 20.03-28.65) (AHF). In both cohorts, AKI was associated with decreased estimated glomerular filtration rate at baseline, chronic kidney disease (UC: RR 1.80 (95% CI 1.15-2.80), AHF: RR 1.51 (95% CI 1.26-1.95) and hypertension (UC: RR 1.30 (95% CI 1.09-1.56), AHF: RR 1.07 (95% CI 1.05-1.09). RRs of AKI in patients on renin-angiotensin-inhibitors were 0.87 (95% CI 0.78-0.97) and 0.88 (95% CI 0.78-0.98) in UC and AHF, respectively. AKI was consistently associated with increased risk of in-hospital mortality (UC: RR 3.15 (95% CI 2.28-4.35), AHF: RR 4.28 (95% CI 2.53-7.24). AKI is frequent in patients ≥ 75years. While reduced renal function at baseline, CKD and hypertension were associated with AKI development, renin-angiotensin-inhibitors may be protective. Older AKI patients showed higher short-term mortality rates.

Abstract P1117: Transcriptional Changes In Failing Hearts In A South Asian Cohort Capture Molecular Pathophysiology Underlying Maladaptive Remodelling And Reflect A Consistent Disease Gene Signature

Heart failure (HF) is a leading cause of death worldwide and research focused on human cardiac tissue provides insights into underlying disease mechanisms. In this study, we performed transcriptome analyses on cardiac tissue from 21 South Asian (SA) HF patients and compared them with 21 controls without HF. The aim was to i) probe dysregulated genes and pathways in HF and ii) identify a core HF gene signature conserved across etiologies and ethnicities. Gene set enrichment analyses on dysregulated genes (DGs) showed positive enrichment of Gene Ontology terms for ECM remodelling, immune signalling and negative enrichment of terms like cardiac conduction, muscle contraction reflecting altered molecular signalling and cellular cross-talk in failing hearts. The immune cell signatures among the DGs suggest changes in immune milieu which correlates with altered immune signalling pathways. Although poor concordance in DGs across studies on HF transcriptome is well documented, evidence on stratification potential of select DGs is still preliminary. Using an independent component analysis and a machine learning based workflow, we identified gene signatures from two cohorts (SA, GSE116250) independently. We refined these into a core signature after cross validating their stratification potential and by removing the genes with low potential. The core signature effectively separated HF from control samples in SA, GSE116250 and other cohorts potentially reflecting central elements underlying end stage HF. In summary, the transcriptome analyses from SA HF cohort highlights the pathways reflecting HF pathophysiology and reiterates conserved themes across public HF cohorts.

Physical activity, sedentary behaviors and all-cause mortality in patients with heart failure: Findings from the NHANES 2007-2014.

BackgroundLimited data are available examining the effects of both moderate- and vigorous-intensity physical activity (MVPA) and sedentary behavior (SB) on longevity among patients with heart failure (HF). This study examined the associations of MVPA and SB with all-cause mortality in HF patients using a nationally representative survey data.MethodsNational Health and Nutrition Examination Survey data (2007–2014) were used. 711 adults with self-reported congestive HF, linked to 2015 mortality data were analyzed. Self-reported MVPA and SB minutes were used to create the three MVPA [No-MVPA, insufficient (I-MVPA; <150 min/wk), and sufficient (S-MVPA; ≥150 min/wk)] and two SB (<8 and ≥8 hrs/d) groups. Cox proportional hazard models were constructed to test the associations of MVPA and SB with all-cause mortality.Results119 deaths occurred over an average of 4.9 years of follow-up. Lower MVPA and higher SB were independently associated with poor survival (P < .001). Joint and stratified analyses showed that the protective effect of MVPA was most pronounced among patients with SB<8 hrs/d. There was no difference in the mortality risk by SB levels within I-MVPA and S-MVPA groups; however, in the No-MVPA group, those with SB≥8 hrs/d had a greater risk of mortality compared to those with <8 hrs/d (Hazard ratio = 1.60).ConclusionIn this HF cohort, MVPA and SB were independently and jointly associated with all-cause mortality. The beneficial effect of MVPA is attenuated by excessive SB; however, engaging in some amount of MVPA may provide a protective effect and attenuates the detrimental effects associated with excessive SB.

A novel approach to attribute responsible physicians using inpatient claims.

More robust attribution methods are necessary to understand physician-level variation in quality of care across risk-adjusted inpatient measures. We address a gap in the literature involving attribution of physicians to inpatient stays using administrative claims data, in which rule-based methods often inadequately attribute physicians. Methodology comparison study using a cross-section of inpatient stays. A novel approach is proposed in which physicians' relative degrees of responsibility for inpatient stays are expressed through physician-specific attribution ratios informed by existing patient characteristics and comorbidities. Attribution results are compared with the rule-based benchmark method for 7 CMS-defined clinical cohorts, including a COVID-19 cohort. Using 6,835,460 unique patient encounters during 2020 (n = 136,339 in out-of-sample cohort), the proposed approach favored specialists generally considered responsible for primary clinical conditions when compared with the benchmark. The most salient shift within the acute myocardial infarction (+17.0%), heart failure (+20.2%), and coronary artery bypass graft (+4.0%) cohorts was toward the cardiovascular diseases specialty, and the chronic obstructive pulmonary disease (+24.0%) and pneumonia (+16.2%) cohorts resulted in a shift toward the pulmonary diseases specialty. The COVID-19 cohort resulted in considerable shifts toward infectious diseases and pulmonary diseases specialties (+17.4% and +14.1%, respectively). The stroke cohort experienced a considerable shift toward the neurology specialty (+42.2%). We provide a robust method to attribute physicians to patients, which is a necessary tool to understand physician-level variation in quality of care within the inpatient acute care setting. The proposed method provides consistency across facilities and eliminates unattributed patients resulting from unsatisfied business rules.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study: prognostic value of cardiac magnetic resonance-derived right ventricular parameters substudy.

Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF). Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan-Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560-1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09-1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function. RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.

Risk factors of short-term, intermediate-term, and long-term cardiac events in patients hospitalized for HFmrEF.

Clinical data on the prognostic determinants over varying periods within the same cohort of heart failure with mid-range or mildly reduced ejection fraction (HFmrEF) remain scarce. This study aimed to identify the short-term, intermediate-term, and long-term risk factors of adverse cardiovascular (CV) outcomes in patients hospitalized for HFmrEF. This retrospective study included 1691 consecutive HFmrEF patients admitted to our hospital between January 2015 and August 2020. Baseline data including clinical characteristics, laboratory and cardiac imaging examinations were obtained. Patients completed at least 1year clinical follow-up after discharge by telephone interview, clinical visit, or community visit. The primary endpoint was defined as a composite of CV death or rehospitalization for heart failure (CV events) at 3, 12, and 33months after the diagnosis of HFmrEF. Mean age of the whole cohort was 69 (61-77) years and 64.8% were male. The median clinical follow-up was 33 (20-50) months. CV events were 17.5%, 28.2%, and 57.8% at 3, 12, and 33months after discharge, respectively. Independent risk factors for CV events were uric acid >382μmol/L, creatinine >100μmol/L, N-terminal pro-B type natriuretic peptide (NT-proBNP)>3368pg/mL and haemoglobin <120g/L for men and <110g/L for women at 3 and 12months. Pulmonary artery systolic pressure >35mmHg and the ratio of early transmitral flow velocity to early mitral annular velocity >18 served as independent risk factors for CV events at 12months. At 33months, uric acid > 382μmol/L, NT-proBNP >3368pg/mL, and pulmonary artery systolic pressure >35mmHg were the independent risk factors of CV events. Higher uric acid, creatinine, NT-proBNP, and lower haemoglobin levels at baseline are valuable serum biomarkers for risk stratification of short-term and long-term CV outcomes of HFmrEF patients. Future studies are needed to verify if intensive heart failure therapy for identified high-risk HFmrEF patients based on these four serum biomarkers could improve their short-term and long-term CV outcomes or not.

Usefulness of C2HEST Score in Predicting Clinical Outcomes of COVID-19 in Heart Failure and Non-Heart-Failure Cohorts.

Background: Patients with heart failure represent a vulnerable population for COVID-19 and are prone to having worse prognoses and higher fatality rates. Still, the clinical course of the infection is dynamic, and complication occurrence in particular in patients with heart failure is fairly unpredictable. Considering that individual components of the C2HEST (C2: Coronary Artery Diseases (CAD)/Chronic obstructive pulmonary disease (COPD); H: Hypertension; E: Elderly (Age ≥ 75); S: Systolic HF; T: Thyroid disease) are parallel to COVID-19 mortality risk factors, we evaluate the predictive value of C2HEST score in patients with heart failure (HF) Material and Methods: The retrospective medical data analysis of 2184 COVID-19 patients hospitalized in the University Hospital in Wroclaw between February 2020 and June 2021 was the basis of the study. The measured outcomes included: in-hospital mortality, 3-month and 6-month all-cause-mortality, non-fatal end of hospitalization, and adverse in-hospital clinical events. Results: The heart failure cohort consists of 255 patients, while 1929 patients were assigned to the non-HF cohort. The in-hospital, 3-month, and 6-month mortality rates were highest in the HF cohort high-risk C2HEST stratum, reaching 38.61%, 53.96%, and 65.36%, respectively. In the non-HF cohort, in-hospital, 3-month, and 6-month mortalities were also highest in the high-risk C2HEST stratum and came to 26.39%, 52.78%, and 65.0%, respectively. An additional point in the C2HEST score increased the total death intensity in 10% of HF subjects (HR 1.100, 95% CI 0.968–1.250 p = 0.143) while in the non-HF cohort, the same value increased by 62.3% (HR 1.623, 95% CI 1.518–1.734 p < 0.0001). Conclusions: The C2HEST score risk in the HF cohort failed to show discriminatory performance in terms of mortality and other clinical adverse outcomes during hospitalization. C2HEST score in the non-HF cohort showed significantly better performance in terms of predicting in-hospital and 6-month mortality and other non-fatal clinical outcomes such as cardiovascular events (myocardial injury, acute heart failure, myocardial infarction, cardiogenic shock), pneumonia, sepsis, and acute renal injury.

Distinct pathophysiological pathways in women and men with heart failure.

Clinical differences between women and men have been described in heart failure (HF). However, less is known about the underlying pathophysiological mechanisms. In this study, we compared multiple circulating biomarkers to gain better insights into differential HF pathophysiology between women and men. In 537 women and 1485 men with HF, we compared differential expression of a panel of 363 biomarkers. Then, we performed a pathway over-representation analysis to identify differential biological pathways in women and men. Findings were validated in an independent HF cohort (575 women, 1123 men). In both cohorts, women were older and had higher left ventricular ejection fraction (LVEF). In the index and validation cohorts respectively, we found 14/363 and 12/363 biomarkers that were relatively up-regulated in women, while 21/363 and 14/363 were up-regulated in men. In both cohorts, the strongest up-regulated biomarkers in women were leptin and fatty acid binding protein-4, compared to matrix metalloproteinase-3 in men. Similar findings were replicated in a subset of patients from both cohorts matched by age and LVEF. Pathway over-representation analysis revealed increased activity of pathways associated with lipid metabolism in women, and neuro-inflammatory response in men (all p &lt; 0.0001). In two independent cohorts of HF patients, biomarkers associated with lipid metabolic pathways were observed in women, while biomarkers associated with neuro-inflammatory response were more active in men. Differences in inflammatory and metabolic pathways may contribute to sex differences in clinical phenotype observed in HF, and provide useful insights towards development of tailored HF therapies.

Survival analysis of a large Belgian heart failure cohort with reduced ejection fraction

The therapeutic management of heart failure has evolved over the past 20 years. Indeed, before 1997, patients with heart failure with reduced ejection fraction (HFrEF) were mainly treated with angiotensin-converting enzyme inhibitors (ACEi). After 1997, several clinical trials demonstrated the benefit of beta-blockers and from 2012, the use of mineralocorticoid receptor antagonists (MRAs) were recommended by AHA guidelines. We prupose to evaluate and analyze clinical characteristics, treatment evolution and long-term outcomes in a large cohort of HFrEF ≤ 35%. Three time periods based on changes in clinical practice according to HF guidelines were defined. Between 1994 and 2020, 2512 patients were included at St-Luc University Hospital at the time of diagnosis of HFrEF and prospectively followed for a primary endpoint of all-cause mortality at 5 years. Patients were classified and compared according to the time of enrolment (group 1: before 1997, group 2: 1997–2012, group 3: 2013–2020). All-cause mortality was analysed using univariate Cox regression analysis. Of the 2512 patients, 67 patients were included in group 1, 1805 in group 2 and 640 in group 3. Patients in groups 2 and 3 were significantly older, had more comorbidities such as hypertension and chronic obstructive pulmonary disease than patients in group 1 ( Table 1 ). Over time, the prevalence of ischemic heart disease decreased and the use of beta-blockers and MRAs increased. A total of 925 (37%) patients died after five years. After adjustment for age and ischaemic etiology, 5-year all-cause mortality was lower in group 2 (HR: 0.41, 95% CI: 0.29 to 0.58, P ≤ 0.001) and group 3 (HR: 0.43, 95% CI: 0.30 to 0.61, P ≤ 0.001) compared to group 1 ( Fig. 1 ). In heart failure with reduced ejection fraction, a significant improvement in survival was observed over the last 20 years, clearly related to better therapeutic management.

BERENICE Final Analysis: Cardiac Safety Study of Neoadjuvant Pertuzumab, Trastuzumab, and Chemotherapy Followed by Adjuvant Pertuzumab and Trastuzumab in HER2-Positive Early Breast Cancer.

Simple SummaryA combination of pertuzumab, trastuzumab, and chemotherapy is a standard treatment for patients with a type of breast cancer called HER2-positive. Before the BERENICE study, little was known about the safety and effectiveness of pertuzumab with trastuzumab after surgery. Cardiac safety was a particular concern, especially when the chemotherapy given before surgery included drugs called anthracyclines. BERENICE was designed to assess the cardiac safety of pertuzumab with trastuzumab before surgery in combination with two different types of anthracycline-based chemotherapies. This paper describes additional safety and effectiveness data from BERENICE after patients had undergone surgery and when they had finished treatment. The incidence of cardiac side effects was low regardless of anthracycline use. The cardiac safety of pertuzumab and trastuzumab is now well characterized based on our study and others. Available information supports the use of pertuzumab–trastuzumab-based therapies as a standard treatment in HER2-positive early breast cancer.BERENICE (NCT02132949) assessed the cardiac safety of the neoadjuvant–adjuvant pertuzumab–trastuzumab-based therapy for high-risk, HER2-positive early breast cancer (EBC). We describe key secondary objectives at final analysis. Eligible patients received dose-dense doxorubicin and cyclophosphamide q2w × 4 ➝ paclitaxel qw × 12 (Cohort A) or 5-fluorouracil, epirubicin, cyclophosphamide q3w × 4 ➝ docetaxel q3w × 4 (B) as per physician’s choice. Pertuzumab–trastuzumab (q3w) was initiated from the taxane start and continued post-surgery to complete 1 year. Median follow-up: 64.5 months. There were no new cardiac issues and a low incidence of Class III/IV heart failure (Cohort B only: one patient (0.5%) in the adjuvant and treatment-free follow-up (TFFU) periods). Fourteen patients (7.7%) had LVEF declines of ≥10% points from baseline to <50% in Cohort A, as did 20 (10.5%) in B during the adjuvant period (12 (6.2%) in A and 7 (3.6%) in B during TFFU). The five-year event-free survival rates in Cohorts A and B were 90.8% (95% CI: 86.5, 95.2) and 89.2% (84.8, 93.6), respectively. The five-year overall survival rates were 96.1% (95% CI: 93.3, 98.9) and 93.8% (90.3, 97.2), respectively. The final analysis of BERENICE further supports pertuzumab–trastuzumab-based therapies as standard of care for high-risk, HER2-positive EBC.

Improving clinical trial efficiency using a machine learning-based risk score to enrich study populations.

Prognostic enrichment strategies can make trials more efficient, although potentially at the cost of diminishing external validity. Whether using a risk score to identify a population at increased mortality risk could improve trial efficiency is uncertain. We aimed to assess whether Machine learning Assessment of RisK and EaRly mortality in Heart Failure (MARKER-HF), a previously validated risk score, could improve clinical trial efficiency. Mortality rates and association of MARKER-HF with all-cause death by 1 year were evaluated in four community-based heart failure (HF) and five HF clinical trial cohorts. Sample size required to assess effects of an investigational therapy on mortality was calculated assuming varying underlying MARKER-HF risk and proposed treatment effect profiles. Patients from community-based HF cohorts (n=11 297) had higher observed mortality and MARKER-HF scores than did clinical trial patients (n=13 165) with HF with either reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF). MARKER-HF score was strongly associated with risk of 1-year mortality both in the community (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.44-1.52) and clinical trial cohorts with HFrEF (HR 1.41, 95% CI 1.30-1.54), and HFpEF (HR 1.74, 95% CI 1.53-1.98), per 0.1 increase in MARKER-HF. Using MARKER-HF to identify patients for a hypothetical clinical trial assessing mortality reduction with an intervention, enabled a reduction in sample size required to show benefit. Using a reliable predictor of mortality such as MARKER-HF to enrich clinical trial populations provides a potential strategy to improve efficiency by requiring a smaller sample size to demonstrate a clinical benefit.

Pulmonary Artery Pressure-Guided Telemonitoring Reduced Pulmonary Artery Pressure but Did Not Result in Higher Doses of Guideline-Directed Medical Therapy-Observations from an Advanced Elderly German Heart Failure Cohort.

Introduction: Remote pulmonary artery pressure (PAP)-guided heart failure (HF) therapy for NYHA class III patients has been shown to reduce hospitalizations and increase survival. We aimed to assess whether PAP monitoring allows for the increase in HF directed medication in an elderly German cohort of advanced HF patients already receiving clinically optimized HF medication. Methods: We analyzed PAP and HF medication dosage, including diuretics, in 24 patients (mean age, 76 years) using implanted PAP-sensors during the first 12 months of PAP-guided HF care in an interdisciplinary HF unit. Results: During 12 months of PAP-guided HF therapy, PAP decreased significantly (△PAP systolic–6 ± 10, △PAP diastolic–4 ± 7, △PAP mean–4 ± 8 mm Hg, p < 0.01 for all). 16% of patients had an unplanned HF hospitalization. There was no significant change over time with respect to the dosage of RAAS inhibitors (ACE-I/ARB/ARNI), Beta blockers, or MRA treatments. In contrast, the dosage of loop diuretics increased significantly (2.1 ± 0.5-fold) over time. In the comparison of a “responder” (patients with PAP and diuretic dose decline) and “non-responder” (patients with PAP and diuretic dose increase) group, there were no significant differences between any of the baseline, medication, or HF hospitalization characteristics between the two groups. Conclusions: In elderly patients treated with clinically optimized HF medication, no further evidence-based medication increase could be achieved using PAP-guided HF care. However, by individual adjustment of diuretic dosage, a significant decline in PAP over time occurred, which could not be predicted by any of the baseline characteristics.

S-ICD in heart failure patients: real-world data from a multicenter, european analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Data on patients with heart failure (HF) and subcutaneous implantable cardioverter defibrillator (S-ICD) are very scarce and limited to a single prospective analysis from the UNTOUCHED trial. Purpose Aim of this study was to assess clinical outcomes of the S-ICD in HF patients, comparing them with a no-HF population, in a real-world analysis from the largest European retrospective S-ICD registry (ELISIR registry). Methods All consecutive patients undergoing S-ICD implantation at 20 European institutions enrolled in the ELISIR registry were used for the current analysis. According to European Guidelines, the registry population was classified into two groups: the HF cohort (further classified as HF with reduced and mid-range ejection fraction – HFrEF and HFmrEF) vs the no-HF group. The primary outcome of the study was the inappropriate shock (IS) rate across the two cohorts. As secondary outcomes, appropriate shocks, cardiovascular mortality and device-related complications during follow-up were assessed. Results A total of 1409 patients from the ELISIR registry were included in this analysis; HF patients represented 57.3% of the entire cohort (n=701, 86.9% HFrEF; n=106,13.1% HFmrEF). As expected, the HF cohort showed significantly higher rates of cardiovascular risk factors and comorbidities when compared to the no-HF cohort. Over a median follow-up of approximately 2 years, a total of 133 inappropriate shocks were observed in the entire cohort, without significant differences among the two groups (9.2% vs 9.8%, p=0.689). 133 complex ventricular arrhythmias were adequately recognized and treated in the overall cohort, showing similar rates of appropriate shocks (9.2% vs 9.8%, p=0.689). Inappropriate and effective shocks-free survival has been represented in Figure 1, showing Kaplan-Meier estimates comparing HF vs no-HF patients, also stratified by left ventricular ejection fraction (LVEF). The impact of baseline and procedural characteristics on the primary outcome was tested through univariable and multivariable Cox regression analysis in HF patients; at multivariate analysis, only age (HR=0.974 [0.955–0.992], p=0.005), LVEF (HR=0.954 [0.926-0.984], p=0.003), ARVC (HR=3.364 [1.206-9.384], p=0.020) and smart pass algorithm "on" (HR=0.321 [0.184-0.560], p&amp;lt;0.001) remained associated with inappropriate shocks (Figure 2). A low number of patients (n=76) experienced device-related complications, more frequently in the HF cohort (6.2% vs 3.8%, p=0.031) with no significant differences regarding any specific outcome of interest: lead infection (1.1% vs 0.7%, p=0.381), pocket infection (1.9% vs 0.8%, p=0.107), pocket hematoma (3.2% vs 2.8%, p=0.668). Conclusion The rate of inappropriate shocks seems to be comparable in both HF and non-HF patients implanted with S-ICD. However, the rate of device-related complications was slightly more frequent in HF patients.