When to use spironolactone, eplerenone or finerenone in the spectrum of cardiorenal diseases.

Kidney disease frequently coexists with cardiovascular (CV) diseases, and this dual presence significantly amplifies the risk of adverse clinical outcomes. Shared pathophysiological mechanisms and common CV risk factors contribute to the increased expression of mineralocorticoid receptors, which in turn can drive the progression of chronic CV-kidney disorders. The steroidal mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone have demonstrated efficacy in improving patient outcomes in cases of heart failure with reduced ejection fraction or after a myocardial infarction, but have limited value in patients with chronic kidney disease. The non-steroidal MRA finerenone has now established itself as a foundational guideline-recommended therapy in patients with diabetic kidney disease. To date, these pharmacological agents have been developed in distinct patient populations. The consequences of their distinct pharmacological profiles necessitate further consideration. They have not undergone testing across the entire spectrum of cardiorenal scenarios, and the evidence base is currently being complemented with ongoing trials. In this review, we aim to synthesize the existing body of evidence and chart the future trajectory for the use of spironolactone, eplerenone and finerenone in improving clinical outcomes across the diverse spectrum of cardiorenal diseases. By consolidating the current state of knowledge, we seek to provide valuable insights for informed decision making in the management of patients with these complex and interconnected conditions.

Validation of the MEDIA echo score for the prognosis of heart failure with preserved ejection fraction.

There is currently no widely used prognostic score in heart failure (HF) with preserved ejection fraction (HFpEF). The MEDIA echo score, including four variables (pulmonary arterial systolic pressure > 40 mmHg, inferior vena cava collapsibility index < 50%, average E/e' > 9, and lateral mitral annular s' < 7 cm/s), has been proposed as a useful risk stratification tool. This study aimed at further validating the MEDIA echo score in both hospitalised and ambulatory HFpEF patients. The MEDIA echo score ranges from 0 to 4 (each criterion scores 1 point). The associations between MEDIA echo score and cardiovascular outcomes were assessed in two independent HFpEF cohorts, namely patients hospitalised for worsening HFpEF (N = 242, mean age 78 ± 11), and stable ambulatory HFpEF patients (N = 76, mean age 65 ± 8). Using multivariable Cox models, in the worsening HFpEF cohort, patients with a MEDIA echo score of 3-4 displayed a significant increased risk of death (HR 2.10, 95%CI 1.02-4.33, P = 0.043, score 0-1 as reference). In the ambulatory HFpEF cohort, patients with a MEDIA echo score of 2 had a significantly higher risk of death or HF hospitalisation (HR 3.44, 95%CI 1.27-9.30, P = 0.015, score 0 as reference), driven by HF hospitalisation; in that cohort, adding the MEDIA echo score to the clinical model significantly improved reclassification for the combined endpoint (integrated discrimination improvement 6.2%, P = 0.006). The MEDIA echo score significantly predicted the outcome of HFpEF patients in both hospital and ambulatory settings; its use may help refine routine risk stratification on top of well-established prognosticators in stable HFpEF patients.

Comparison between the diagnostic performance of vessel fractional flow reserve and nonhyperemic pressure ratio for functionally significant coronary stenosis severity as assessed by fractional flow reserve.

BACKGROUND: Fractional flow reserve (FFR) and nonhyperemic pressure ratios (NHPRs) have been widely used to assess the functional severity of coronary stenosis. However, their measurement requires using a pressure wire, making their use in all patients difficult. The recently developed vessel fractional flow reserve (vFFR), derived from three-dimensional quantitative coronary angiography, is expected to serve as a surrogate for pressure wire assessment. METHODS: This retrospective study was conducted on patients with intermediate coronary stenosis who underwent FFR and NHPR measurements. The vFFR and NHPR values were compared for diagnosing coronary stenosis as defined by an FFR of ≤0.80, and the number of patients not requiring wire-based assessment was estimated. RESULTS: In a total of 90 lesions from 74 patients (median [SD] age 75 [12] years; men 80%), the median FFR was 0.78 (0.72-0.84), and 57% of these lesions (N = 51) exhibited an FFR of ≤0.80. vFFR provided high discrimination for coronary stenosis (area under the curve 0.80, 95% confidence interval 0.70-0.90), which was comparable to that of NHPRs (p = 0.42). High diagnostic accuracy was consistently observed across a variety of clinical presentations (i.e., old age, diabetes, target coronary artery, and left ventricular hypertrophy) (pinteraction > 0.05). In total, 55 lesions (61%) demonstrated positive or negative likelihood of coronary stenosis when vFFR was <0.73 (specificity 90%) or >0.87 (sensitivity 88%), respectively. CONCLUSION: vFFR demonstrated excellent diagnostic performance for detecting functionally significant coronary stenosis as evaluated by FFR. vFFR may be used as a surrogate for pressure wire assessment.

Inductive database to support iterative data mining: Application to biomarker analysis on patient data in the Fight-HF project.

Machine learning is now an essential part of any biomedical study but its integration into real effective Learning Health Systems, including the whole process of Knowledge Discovery from Data (KDD), is not yet realised. We propose an original extension of the KDD process model that involves an inductive database. We designed for the first time a generic model of Inductive Clinical DataBase (ICDB) aimed at hosting both patient data and learned models. We report experiments conducted on patient data in the frame of a project dedicated to fight heart failure. The results show how the ICDB approach allows to identify biomarker combinations, specific and predictive of heart fibrosis phenotype, that put forward hypotheses relative to underlying mechanisms. Two main scenarios were considered, a local-to-global KDD scenario and a trans-cohort alignment scenario. This promising proof of concept enables us to draw the contours of a next-generation Knowledge Discovery Environment (KDE).

Correction: Diagnostic performance of congestion score index evaluated from chest radiography for acute heart failure in the emergency department: A retrospective analysis from the PARADISE cohort.

[This corrects the article DOI: 10.1371/journal.pmed.1003419.].

Diagnostic performance of congestion score index evaluated from chest radiography for acute heart failure in the emergency department: A retrospective analysis from the PARADISE cohort.

BACKGROUND: Congestion score index (CSI), a semiquantitative evaluation of congestion on chest radiography (CXR), is associated with outcome in patients with heart failure (HF). However, its diagnostic value in patients admitted for acute dyspnea has yet to be evaluated. METHODS AND FINDINGS: The diagnostic value of CSI for acute HF (AHF; adjudicated from patients' discharge files) was studied in the Pathway of dyspneic patients in Emergency (PARADISE) cohort, including patients aged 18 years or older admitted for acute dyspnea in the emergency department (ED) of the Nancy University Hospital (France) between January 1, 2015 and December 31, 2015. CSI (ranging from 0 to 3) was evaluated using a semiquantitative method on CXR in consecutive patients admitted for acute dyspnea in the ED. Results were validated in independent cohorts (N = 224). Of 1,333 patients, mean (standard deviation [SD]) age was 72.0 (18.5) years, 686 (51.5%) were men, and mean (SD) CSI was 1.42 (0.79). Patients with higher CSI had more cardiovascular comorbidities, more severe congestion, higher b-type natriuretic peptide (BNP), poorer renal function, and more respiratory acidosis. AHF was diagnosed in 289 (21.7%) patients. CSI was significantly associated with AHF diagnosis (adjusted odds ratio [OR] for 0.1 unit CSI increase 1.19, 95% CI 1.16-1.22, p < 0.001) after adjustment for clinical-based diagnostic score including age, comorbidity burden, dyspnea, and clinical congestion. The diagnostic accuracy of CSI for AHF was >0.80, whether alone (area under the receiver operating characteristic curve [AUROC] 0.84, 95% CI 0.82-0.86) or in addition to the clinical model (AUROC 0.87, 95% CI 0.85-0.90). CSI improved diagnostic accuracy on top of clinical variables (net reclassification improvement [NRI] = 94.9%) and clinical variables plus BNP (NRI = 55.0%). Similar diagnostic accuracy was observed in the validation cohorts (AUROC 0.75, 95% CI 0.68-0.82). The key limitation of our derivation cohort was its single-center and retrospective nature, which was counterbalanced by the validation in the independent cohorts. CONCLUSIONS: In this study, we observed that a systematic semiquantified assessment of radiographic pulmonary congestion showed high diagnostic value for AHF in dyspneic patients. Better use of CXR may provide an inexpensive, widely, and readily available method for AHF triage in the ED.

Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure).

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes.Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression.Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism.Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significanceMore insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolismBiomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials.Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.

Cardiovascular Comorbidities Are the Main Predictors of Cardiac Reverse Remodeling following Kidney Transplantation.

BACKGROUND: End-stage renal disease is associated with cardiac remodeling, which is partly reversible after kidney transplantation (KT). We aimed to determine the association of cardiovascular comorbidities or kidney-related factors with cardiac reverse remodeling after KT. METHODS: We performed echocardiography in 56 patients (aged 48 ± 15 years, mean ± SD) before and 24 months after undergoing their first KT. Echocardiograms were reviewed using a standardized process with blinding for the patient characteristics and evaluation timing. Multivariable linear regression analysis was used to evaluate the association between comorbidities and changes in cardiac structure and systolic/diastolic function. RESULTS: Left ventricular mass index (LVMI) and diastolic parameters did not change significantly, while left ventricular ejection fraction (LVEF) increased from 63.9 to 69.6% (p = 0.046). Multivariable analysis revealed associations of histories of valvular heart disease with a smaller reduction in LVMI (ß = -27.3, p = 0.04), of coronary artery disease or heart failure with a smaller increase in LVEF (ß = 7.17, p = 0.02), and of diabetes mellitus with less improvement in E wave (ß = -0.19, p = 0.05), e' (ß = 4.15, p = 0.046), and E/e' (ß = -5.00, p < 0.01). CONCLUSION: Cardiovascular comorbidities were -associated with less improvement in cardiac structure and function following KT. Our findings suggest that patients with CV comorbidities may experience limited "favorable" reverse cardiac remodeling following KT.

Older age is associated with greater central aortic blood pressure following the exercise stress test in subjects with similar brachial systolic blood pressure.

Brachial systolic pressure (BSP) is often monitored during exercise by the stress test; however, central systolic pressure (CSP) is thought to be a more direct measure of cardiovascular events. Although some studies reported that exercise and aging may play roles in changes of both BSP and CSP, the relationship between BSP and CSP with age following the exercise stress test remains unclear. The aim of this study was to evaluate the effect of age on the relationship between BSP and CSP measured after exercise. Ninety-six subjects underwent the diagnostic treadmill exercise stress test, and we retrospectively divided them into the following 3 groups by age: the younger age group (43 ± 4 years), middle age group (58 ± 4 years), and older age group (70 ± 4 years). Subjects exercised according to the Bruce protocol, to achieve 85 % of their age-predicted maximum heart rate or until the appearance of exercise-associated symptoms. BSP, CSP, and pulse rate (PR) were measured using a HEM-9000AI (Omron Healthcare, Japan) at rest and after exercise. BSP, CSP, and PR at rest were not significantly different among the 3 groups (p = 0.92, 0.21, and 0.99, respectively). BSP and PR immediately after exercise were not significantly different among the groups (p = 0.70 and 0.38, respectively). However, CSP immediately after exercise was 144 ± 18 mmHg (younger age), 149 ± 17 mmHg (middle age), and 158 ± 19 mmHg (older age). CSP in the older age group was significantly higher than that in the younger age group (p < 0.01). Despite similar BSPs in all age groups after exercise, CSP was higher in the older age group. Therefore, older subjects have a higher CSP after exercise, which is not readily assessed by conventional measurements of BSP.

Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase.

Neuromyelitis optica (NMO) is a severe inflammatory demyelinating disease with exacerbations involving recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis. Pulse steroid therapy is recommended as the initial, acute-phase treatment for NMO. If ineffective, treatment with plasma exchange (PE) should commence. However, no evidence exists to support the effectiveness of PE long after the acute phase. Immunoadsorption therapy (IA) eliminates pathogenic antibodies while sparing other plasma proteins. With IA, side effects of PE resulting from protein substitution can be avoided. However, whether IA is effective for NMO remains unclear. We describe a patient with anti-aquaporin-4-positive myelitis who responded to IA using a tryptophan polyvinyl alcohol gel column that was begun 52 days after disease onset following the acute phase. Even long after the acute phase when symptoms appear to be stable, IA may be effective and should not be excluded as a treatment choice.

Artificial intelligence-derived left ventricular strain in echocardiography in patients treated with chemotherapy.

Global longitudinal strain (GLS) is an echocardiographic measure to detect chemotherapy-related cardiovascular dysfunction. However, its limited availability and the needed expertise may restrict its generalization. Artificial intelligence (AI)-based GLS might overcome these challenges. Our aims are to explore the agreements between AI-based GLS and conventional GLS, and to assess whether the agreements were influenced by expertise levels, cardiac remodeling and cardiovascular diseases/risks. Echocardiographic images in the apical four-chamber view of left ventricle were retrospectively analyzed based on AI-based GLS in patients treated with chemotherapy, and correlation between AI-based GLS (Caas Qardia, Pie Medical Imaging) and conventional GLS (Vivid E9/VividE95, GE Healthcare) were assessed. The agreement between unexperienced physicians ("GLS beginner") and experienced echocardiographer were also assessed. Among 94 patients (mean age 69 ± 12 years, 73% female), mean left ventricular ejection fraction was 64 ± 6%, 14% of patients had left ventricular hypertrophy, and 21% had left atrial enlargement. Mean GLS was - 15.9 ± 3.4% and - 19.0 ± 3.7% for the AI and conventional method, respectively. There was a moderate correlation between these methods (rho = 0.74; p < 0.01), and bias was - 3.1% (95% limits of agreement: -8.1 to 2.0). The reproducibility between GLS beginner and an experienced echocardiographer was numerically better in the AI method than the conventional method (inter-observer agreement = 0.82 vs. 0.68). The agreements were consistent across abnormal cardiac structure and function categories (p-for-interaction > 0.10). In patients treated with chemotherapy. AI-based GLS was moderately correlated with conventional GLS and provided a numerically better reproducibility compared with conventional GLS, regardless of different levels of expertise.

Adverse events associated with early initiation of Eplerenone in patients hospitalized for acute heart failure.

BACKGROUND: The guidelines recommend the initiation or up-titration of heart failure (HF) treatments following an HF hospitalization; however, concerns about adverse events may limit the use of mineralocorticoid receptor antagonists (MRAs). Patient profiles or disease severity might impact adverse events associated with MRA therapy in acute HF. METHODS: The EARLIER trial included patients with acute HF who were randomized to eplerenone or placebo over 6 months. Adverse events (i.e., worsening renal function [WRF], hyperkalemia, hypotension, and volume depletion/dehydration) were assessed. HF-related outcome included a composite of all-cause mortality, HF re-hospitalization, investigator-reported worsening HF and out-of-hospital diuretic intensification. RESULTS: In 297 patients (mean age: 67 ± 13 years; 73% males), adverse events were observed: 44.4% experienced WRF (>20% drop in estimated glomerular filtration rate[eGFR] and/or investigator-reported WRF), 8.4% had hyperkalemia (potassium >5.5 mmol/L and/or investigator-reported hyperkalemia), 27.9% experienced hypotension (systolic blood pressure[SBP] <90 mmHg and/or investigator-reported hypotension), and 16.8% had investigator-reported volume depletion/dehydration. Eplerenone vs. placebo did not elevate the incidence of these events (all-p-values>0.0 5). Multivariable analyses revealed that, irrespective of treatment allocation, older age (>7 5 years), prevalent diabetes, symptomatic congestion, and microalbuminuria were associated with increased risk of WRF. Baseline eGFR<60 ml/min/1.73m2 and SBP < 90 mmHg predicted hyperkalemia and hypotension, respectively, while older patients were more likely to experience volume depletion/dehydration. However, these patient profiles did not alter the benefit of eplerenone on outcomes (HR [9 5%CI] = 0.53 [0.29 to 0.97], P = 0.04; all-p-for-interaction>0.10). CONCLUSION: Eplerenone did not increase adverse events compared with placebo in acute HF. Importantly, disease severity and comorbidity burden greatly influence adverse events, but not benefit from eplerenone.

Pediatric hypertrophic cardiomyopathy caused by a novel TNNI3 variant.

TNNI3 is a gene that causes hypertrophic cardiomyopathy (HCM). A 14-year-old girl who was diagnosed with nonobstructive HCM presented with cardiopulmonary arrest due to ventricular fibrillation. Genetic testing revealed a novel de novo heterozygous missense variant in TNNI3, NM_000363.5:c.583A>T (p.Ile195Phe), which was determined to be the pathogenic variant. The patient exhibited progressive myocardial fibrosis, left ventricular remodeling, and life-threatening arrhythmias. Genetic testing within families is useful for risk stratification in pediatric HCM patients.

Proteomic profiles of left atrial volume and its influence on response to spironolactone: Findings from the HOMAGE trial and STANISLAS cohort.

AIMS: High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables. METHODS AND RESULTS: In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m2). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population-based cohort (STANISLAS; n = 1640; mean age 49 ± 14 years; women 51%; LAVi 23 ± 7 ml/m2). In both studies, greater LAVi was significantly associated with greater left ventricular masses and volumes. In HOMAGE, after adjustment and correction for multiple testing, greater LAVi was associated with higher concentrations of matrix metallopeptidase-2 (MMP-2), insulin-like growth factor binding protein-2 (IGFBP-2) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (false discovery rates [FDR] <0.05). These associations were externally replicated in STANISLAS (all FDR <0.05). Among these biomarkers, spironolactone decreased concentrations of MMP-2 and NT-proBNP, regardless of baseline LAVi (pinteraction > 0.10). Spironolactone also significantly reduced LAVi, improved left ventricular ejection fraction, lowered E/e', blood pressure and serum procollagen type I C-terminal propeptide (PICP) concentration, a collagen synthesis marker, regardless of baseline LAVi (pinteraction > 0.10). CONCLUSION: In individuals without heart failure, LAVi was associated with MMP-2, IGFBP-2 and NT-proBNP. Spironolactone reduced these biomarker concentrations as well as LAVi and PICP, irrespective of left atrial size.

Effect of eplerenone on clinical stability of Japanese patients with acute heart failure.

BACKGROUND: In the EARLIER (Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure) trial, eplerenone did not reduce heart failure (HF) hospitalizations or all-cause mortality in 300 patients admitted for acute HF (AHF). However, the trial might have been underpowered for these endpoints, and a comprehensive overview of the effect of eplerenone on diuretic doses and patients' clinical stability is warranted. METHODS: The EARLIER trial included Japanese patients hospitalized for AHF randomly assigned to eplerenone or placebo over 6 months. Cox proportional hazards and mixed-effects models were used for analyses. RESULTS: Three hundred patients were included (mean age, 67 ± 13 years; 73% males). The median furosemide equivalent dose was 40 (20-62) mg at randomization. Patients with higher furosemide-equivalent doses had more severe signs and symptoms of congestion and a higher risk of all-cause mortality or HF hospitalization during 6-month follow-up (adjusted-hazard ratio per 10 mg/day increase = 1.25, 95% confidence interval: 1.05-1.49). Eplerenone significantly decreased furosemide-equivalent diuretic doses and b-type natriuretic levels throughout the follow-up (overall-joint-p < 0.05 for both) and reduced E/e' and inferior vena cava diameter at 4 weeks (both p < 0.05). Additionally, eplerenone significantly reduced left ventricular (LV) end-diastolic diameter at 24 weeks (p < 0.05). CONCLUSIONS: Eplerenone treatment improved the clinical stability particularly during short period following hospitalization for AHF, translated by lower diuretic doses, natriuretic peptide levels, indirect markers of filling pressure and venous congestion, and a smaller LV volume.

Associations of childhood adiposity with adult intima-media thickness and inflammation: a 20-year longitudinal population-based cohort.

BACKGROUND: The associations between childhood adiposity and adult increased carotid intima-media thickness (cIMT) have been well established, which might be corroborated by the association between adiposity in children and inflammation in adults. However, longitudinal data regarding biological pathways associated with childhood adiposity are lacking. METHODS: The current study included participants from the STANISLAS cohort who had adiposity measurements at age 5-18 years [ N  = 519, mean (SD) age, 13.0 (2.9) years; 46.4% male], and who were measured with cIMT, vascular-related and metabolic-related proteins at a median follow-up of 19 ±â€Š2 years. BMI, waist-to-height ratio and waist circumference were converted to age-specific and sex-specific z -scores. RESULTS: A minority of children were overweight/obese (16.2% overweight-BMI z -score >1; 1.3% obesity- z -score >2). Higher BMI, waist-height ratio and waist circumference in children were significantly associated with greater adult cIMT in univariable analysis, although not after adjusting for C-reactive protein. These associations were more pronounced in those with consistently high adiposity status from childhood to middle adulthood. Participants with higher adiposity during childhood (BMI or waist-height ratio) had higher levels of insulin-like growth factor-binding protein-1, protein-2, matrix metalloproteinase-3, osteopontin, hemoglobin and C-reactive protein in adulthood. Network analysis showed that IL-6, insulin-like growth factor-1 and fibronectin were the key proteins associated with childhood adiposity. CONCLUSION: In a population-based cohort followed for 20 years, higher BMI or waist-to-height ratio in childhood was significantly associated with greater cIMT and enhanced levels of proteins reflective of inflammation, supporting the importance of inflammation as progressive atherosclerosis in childhood adiposity.

Exercise-induced B-lines for the diagnosis of heart failure with preserved ejection fraction: a two-centre study.

BACKGROUND: Diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging despite the use of scores/algorithms. This study intended to assess the diagnostic value of exercise lung ultrasound (LUS) for HFpEF diagnosis. METHODS: We studied two independent case-control studies of HFpEF patients and control subjects undergoing different exercise protocols: (i) submaximal exercise stress echocardiography (ESE) with LUS performed by expert cardiologists (N = 116, HFpEF = 65.5%), and (ii) maximal cycle ergometer test (CET) (N = 54, HFpEF = 50%) with LUS performed by unexperienced physicians shortly trained for the study. B-line kinetics (i.e. peak values and their changes from rest) were assessed. RESULTS: In the ESE cohort, the C-index (95% CI) of peak B-lines for HFpEF diagnosis was 0.985 (0.968-1.000), whereas the C-index of rest and exercise HFA-PEFF scores (i.e. including stress echo findings) were < 0.90 (CI 0.823-0.949), and that of H2FPEF score was < 0.70 (CI 0.558-0.764). The C-index increase of peak B-lines on top of the above-mentioned scores was significant (C-index increase > 0.090 and P-value < 0.001 for all). Similar results were observed for change B-lines. Peak B-lines > 5 (sensitivity = 93.4%, specificity = 97.5%) and change B-lines > 3 (sensitivity = 94.7%, specificity = 87.5%) were the best cutoffs for HFpEF diagnosis. Adding peak or change B-lines on top of HFpEF scores and BNP significantly improved diagnostic accuracy. Peak B-lines showed a good diagnostic accuracy in the LUS beginner-led CET cohort (C-index = 0.713, 0.588-0.838). CONCLUSIONS: Exercise LUS showed excellent diagnostic value for HFpEF diagnosis regardless of different exercise protocols/level of expertise, with additive diagnostic accuracy on top of available scores and natriuretic peptides.

A machine learning-derived echocardiographic algorithm identifies people at risk of heart failure with distinct cardiac structure, function, and response to spironolactone: Findings from the HOMAGE trial.

AIM: An echocardiographic algorithm derived by machine learning (e'VM) characterizes pre-clinical individuals with different cardiac structure and function, biomarkers, and long-term risk of heart failure (HF). Our aim was the external validation of the e'VM algorithm and to explore whether it may identify subgroups who benefit from spironolactone. METHODS AND RESULTS: The HOMAGE (Heart OMics in AGEing) trial enrolled participants at high risk of developing HF randomly assigned to spironolactone or placebo over 9 months. The e'VM algorithm was applied to 416 participants (mean age 74 ± 7 years, 25% women) with available echocardiographic variables (i.e. e' mean, left ventricular end-diastolic volume and mass indexed by body surface area [LVMi]). The effects of spironolactone on changes in echocardiographic and biomarker variables were assessed across e'VM phenotypes. A majority (>80%) had either a 'diastolic changes' (D), or 'diastolic changes with structural remodelling' (D/S) phenotype. The D/S phenotype had the highest LVMi, left atrial volume, E/e', natriuretic peptide and troponin levels (all p < 0.05). Spironolactone significantly reduced E/e' and B-type natriuretic peptide (BNP) levels in the D/S phenotype (p < 0.01), but not in other phenotypes (p > 0.10; pinteraction <0.05 for both). These interactions were not observed when considering guideline-recommended echocardiographic structural and functional abnormalities. The magnitude of effects of spironolactone on LVMi, left atrial volume and a type I collagen marker was numerically higher in the D/S phenotype than the D phenotype but the interaction test did not reach significance. CONCLUSIONS: In the HOMAGE trial, the e'VM algorithm identified echocardiographic phenotypes with distinct responses to spironolactone as assessed by changes in E/e' and BNP.

Assessment of Patient Knowledge, Awareness, and Adherence in Heart Failure in a Real-Life Setting: Insights from Data Acquired in Pharmacies.

BACKGROUND: Patient knowledge is crucial for managing and/or monitoring patients with heart failure (HF). However, "real-life" evidence of knowledge level and awareness in HF is yet to be explored. We assessed unselected HF patients' knowledge and awareness in a pharmacy setting. METHODS: One hundred eight HF patients (mean age [SD], 70 (12) years, 61% men) were studied in pharmacies in the north-east region of France in 2019. All patients were interviewed by their pharmacist to quantify their knowledge in HF, self-assessment of symptoms of congestion, as well as their adherence to HF treatment and guideline-recommended lifestyle. RESULTS: Overall, 40% of patients had not consulted their cardiologist in the past 6 months, and 89% never underwent an HF education program. Regarding HF knowledge, nearly half were unsure whether they had HF (43.5%). Only half of the patients knew how to self-assess HF symptoms (57.4%), while a quarter (25%) were unsure of the purpose of HF medications. CONCLUSIONS: In patients with HF assessed in their pharmacies, a majority lacked fundamental knowledge regarding HF, such as self-assessment of congestion, possibly due to a minimal proportion of patients undergoing an HF education program. These results suggest that interventions led by pharmacies may help improve HF education coverage in patients who may have poor access to specialized care.