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Abstract Aims In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)‐guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90 days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12 months. Methods and results SIRONA 2 is a prospective, multi‐centre, open‐label, single‐arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N‐terminal pro‐brain natriuretic peptide within 12 months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12 months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9 ± 7.3 mmHg. The device safety profile was excellent with 98.4% freedom from device/system‐related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P

Abstract Aims Transthyretin amyloid cardiomyopathy (ATTR‐CM), a progressive and fatal cardiomyopathy, is frequently misdiagnosed or entails diagnostic delays, hindering patients from timely treatment. This study aimed to generate a systematic framework based on data from electronic health records (EHRs) to assess patients with ATTR‐CM in a real‐world population of heart failure (HF) patients. Predictive factors or combinations of predictive factors related to ATTR‐CM in a European population were also assessed. Methods and results Retrospective unstructured and semi‐structured data from EHRs of patients from OLV Hospital Aalst, Belgium (2012–20), were processed using natural language processing (NLP) to generate an Observational Medical Outcomes Partnership Common Data Model database. NLP model performance was assessed on a random subset of EHRs by comparing algorithm outputs to a physician‐generated standard (using precision, recall, and their harmonic mean, or F1‐score). Of the 3127 HF patients, 103 potentially had ATTR‐CM (age 78 ± 9 years; male 55%; ejection fraction of 48% ± 16). The mean diagnostic delay between HF and ATTR‐CM diagnosis was 1.8 years. Besides HF and cardiomyopathy‐related phenotypes, the strongest cardiac predictor was atrial fibrillation (AF; 72% in ATTR‐CM vs. 60% in non‐ATTR‐CM, P = 0.02), whereas the strongest non‐cardiac predictor was carpal tunnel syndrome (21% in ATTR‐CM vs. 3% in non‐ATTR‐CM, P

Abstract Aims The Cardiovascular Outcomes Retrospective Data analysIS in Heart Failure (CORDIS‐HF) is a single‐centre retrospective study aimed to (i) clinically characterize a real‐world population with heart failure (HF) with reduced (HFrEF) and mildly reduced ejection fraction (HFmrEF), (ii) evaluate impact of renal–metabolic comorbidities on all‐cause mortality and HF readmissions, and (iii) determine patients' eligibility for sodium–glucose cotransporter 2 inhibitors (SGLT2is). Methods and results Using a natural language processing algorithm, clinical data of patients diagnosed with HFrEF or HFmrEF were retrospectively collected from 2014 to 2018. Mortality and HF readmission events were collected during subsequent 1 and 2 year follow‐up periods. The predictive role of patients' baseline characteristics for outcomes of interest was assessed using univariate and multivariate Cox proportional hazard models. Kaplan–Meier analysis was used to determine if type 2 diabetes (T2D) and chronic kidney disease (CKD) impacted mortality and HF readmission rates. The European SGLT2i label criteria were used to assess patients' eligibility. The CORDIS‐HF included 1333 HF patients with left ventricular ejection fraction (LVEF)

Abstract Aims We aim to assess the theoretical impact of the atrial flow regulator (AFR) on survival in heart failure. Methods and results The prospective, multicentre, open‐label, non‐randomised PRELIEVE study (NCT 03030274) assessed the safety and efficacy of the Occlutech AFR device in patients with symptomatic heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction (LVEF) ≥ 15% and

Abstract The inadequacy of medical therapies for heart failure with preserved ejection fraction (HFpEF) is driving the development of device‐based solutions targeting underlying pathophysiologic abnormalities. The maladaptive autonomic imbalance with a reduction in vagal parasympathetic activity and increased sympathetic signalling contributes to the deterioration of cardiac performance, patient fitness, and the increased overall morbidity and mortality. Thoracic aortic vagal afferents mediate parasympathetic signalling, and their stimulation has been postulated to restore autonomic balance. In this first‐in‐man experience with chronic stimulation of aortic vagal afferents (Harmony™ System, Enopace, Israel), we demonstrate improved left atrial remodelling and function parallel with improved left ventricular performance. The observed favourable structural and functional cardiac changes remained stable throughout the 1 year follow‐up and were associated with improved symptoms and physical fitness. The current experience warrants further validation of the endovascular stimulation of aortic thoracic afferents as a new interventional approach for device‐based treatment in HFpEF.

Abstract Aims Implantable pulmonary artery pressure (PAP) sensors have been shown to reduce heart failure hospitalizations (HFH) in selected patients. The goal of this study was to evaluate the safety and efficacy of a novel wireless PAP monitoring system in patients with heart failure (HF). Methods and results This is a prospective, multi‐centre, open‐label, single‐arm trial evaluating the safety and efficacy of the Cordella™ PA Sensor System including the comprehensive Cordella™ Heart Failure System (CHFS) in patients with New York Heart Association (NYHA) Class III heart failure with a heart failure hospitalization and/or increase of N‐terminal pro‐Brain Natriuretic Peptide (NT‐proBNP) within 12 months of enrolment. The primary efficacy endpoint was the accuracy of PA sensor mean PAP measurements, compared with fluid‐filled catheter mean PAP measurements obtained by standard right heart catheterization (RHC) at 90 days post‐implant, assessed in all patients with a successful implant. The primary safety endpoint was freedom from adverse events associated with use of the Cordella PA Sensor System through 30 days post‐implant, assessed in all patients who entered the cath lab for PA sensor implant. The PA sensor was successfully implanted in 70 patients. Equivalence between the PA sensor and RHC for mean pulmonary artery pressures was excellent with measurements confined within the equivalence bounds of −4.0 to 4.0 mmHg (mean PAP: 0.0 to 2.9 mmHg, P = 0.003). The device safety profile was excellent with 98.6% freedom from Device System Related Complications, defined as invasive treatment, device explant or death. There were no pressure sensor failures. Patients' adherence to daily measurement transmissions of PAP and vital signs was 94%. Conclusions This trial supports the safety and efficacy of the Cordella PA Sensor System and in conjunction with the CHFS enables comprehensive HF management in NYHA class III heart failure patients.

Abstract Aims Risk stratification in patients with a new onset or worsened heart failure (HF) is essential for clinical decision making. We have utilized a novel approach to enrich patient level prognostication using longitudinally gathered data to develop ML‐based algorithms predicting all‐cause 30, 90, 180, 360, and 720 day mortality. Methods and results In a cohort of 2449 HF patients hospitalized between 1 January 2011 and 31 December 2017, we utilized 422 parameters derived from 151 451 patient exams. They included clinical phenotyping, ECG, laboratory, echocardiography, catheterization data or percutaneous and surgical interventions reflecting the standard of care as captured in individual electronic records. The development of predictive models consisted of 101 iterations of repeated random subsampling splits into balanced training and validation sets. ML models yielded area under the receiver operating characteristic curve (AUC‐ROC) performance ranging from 0.83 to 0.89 on the outcome‐balanced validation set in predicting all‐cause mortality at aforementioned time‐limits. The 1 year mortality prediction model recorded an AUC of 0.85. We observed stable model performance across all HF phenotypes: HFpEF 0.83 AUC, HFmrEF 0.85 AUC, and HFrEF 0.86 AUC, respectively. Model performance improved when utilizing data from more hospital contacts compared with only data collected at baseline. Conclusions Our findings present a novel, patient‐level, comprehensive ML‐based algorithm for predicting all‐cause mortality in new or worsened heart failure. Its robust performance across phenotypes throughout the longitudinal patient follow‐up suggests its potential in point‐of‐care clinical risk stratification.

Abstract Aims Identification of heart failure (HF) patients with secondary mitral regurgitation (SMR) that benefit from mitral valve (MV) repair remains challenging. We have focused on the role of left ventricular global longitudinal strain (LV‐GLS) and reservoir left atrial longitudinal strain (LASr) for the prediction of long‐term survival and reverse remodelling in patients with SMR undergoing endoscopic MV repair. Methods and results The study population consisted of 110 patients (age 67 ± 11 years, 66% men) with symptomatic SMR undergoing isolated MV repair using a minimally invasive surgical approach. Speckle tracking‐derived LV‐GLS and LASr were assessed in apical views using vendor‐independent software. Over a median of 7.7 years (IQRs 2.9–11.2), 64 patients (58%) died. Significant reverse LV (↓ LVESVI >10 mL/m2), LA (↓ LAVI >10 mL/m2) remodelling or both were observed in 43 (39%), 37 (34%) and 19 (17%) patients, respectively. LV‐GLS (HR 0.68, 95% CI 0.58–0.79, P

Abstract Aims Non‐invasive myocardial work (MW) is a validated index of left ventricular (LV) systolic performance, incorporating afterload and myocardial metabolism. The role of MW in predicting the first hospitalization for de novo heart failure with preserved ejection fraction (HFpEF) is still unknown. We aim to investigate the diagnostic performance of MW to predict the first de novo HFpEF hospitalization in ambulatory individuals with preserved LV ejection fraction. Methods and results Twenty‐nine patients with transthoracic echocardiography performed at least 6 months before the first HFpEF hospitalization were compared with 29 matched controls. MW was derived as the area of pressure–strain loop using speckle‐tracking and brachial artery blood pressure. Global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE) were collected. First HFpEF hospitalization and its combination with cardiovascular death [major adverse cardiovascular events (MACE)] and all‐cause of death [major adverse events (MAE)] were assessed. At baseline, future HFpEF patients showed lower global work index, global constructive work, GWE, and higher GWW than controls (all P 170 mmHg% was associated with a 4‐fold increase of MACE (HR = 4.5, 95% CI 1.59–13.12, P = 0.005) and a 3‐fold higher risk of MAE (HR = 2.9, 95% CI 1.24–6.6, P = 0.014). Conclusions In ambulatory patients with preserved LV ejection fraction and risk factors, GWW showed high accuracy to predict the first HFpEF hospitalization and its combination with mortality. The GWW routine assessment may be clinically helpful in patients with dyspnoea.

Abstract Aims We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). Methods and results In the first stage, 83 HF‐related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age‐matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up‐regulated in non‐survivors vs. survivors (2.40 ± 3.66 vs. 0.36 ± 0.22 units, P 316 μg/mL were associated with increased all‐cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5–3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2–3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N‐terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all‐cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure. Conclusion In patients with a de novo or worsened HF, increased SERPINA3 levels > 316 μg/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF.

Abstract Aims The implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator‐based HeartLogic™ algorithm has recently been developed for early detection of impending decompensation in heart failure (HF) patients; but whether this novel algorithm can reduce HF hospitalizations has not been evaluated. We investigated if activation of the HeartLogic algorithm reduces the number of hospital admissions for decompensated HF in a 1 year post‐activation period as compared with a 1 year pre‐activation period. Methods and results Heart failure patients with an implantable cardiac defibrillator/cardiac resynchronization therapy with defibrillator with the ability to activate HeartLogic and willingness to have remote device monitoring were included in this multicentre non‐blinded single‐arm trial with historical comparison. After a HeartLogic alert, the presence of HF symptoms and signs was evaluated. If there were two or more symptoms and signs apart from the HeartLogic alert, lifestyle advices were given and/or medication was adjusted. After activation of the algorithm, patients were followed for 1 year. HF events occurring in the 1 year prior to activation and in the 1 year after activation were compared. Of the 74 eligible patients (67.2 ± 10.3 years, 84% male), 68 patients completed the 1 year follow‐up period. The total number of HF hospitalizations reduced from 27 in the pre‐activation period to 7 in the post‐activation period (P = 0.003). The number of patients hospitalized for HF declined from 21 to 7 (P = 0.005), and the hospitalization length of stay diminished from average 16 to 7 days (P = 0.079). Subgroup analysis showed similar results (P = 0.888) for patients receiving cardiac resynchronization therapy during the pre‐activation period or not receiving cardiac resynchronization therapy, meaning that the effect of hospitalizations cannot solely be attributed to reverse remodelling. Subanalysis of a single‐centre Belgian subpopulation showed important reductions in overall health economic costs (P = 0.025). Conclusion Activation of the HeartLogic algorithm enables remote monitoring of HF patients, coincides with a significant reduction in hospitalizations for decompensated HF, and results in health economic benefits.

Abstract Aims This study aims to explore long‐term clinical outcomes of cardiopoiesis‐guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART‐1) trial. Methods and results CHART‐1 is a multinational, randomized, and double‐blind trial conducted in 39 centres in heart failure patients (n = 315) on standard‐of‐care therapy. The ‘active’ group received cardiopoietic stem cells delivered intramyocardially using a retention‐enhanced catheter. The ‘control’ group underwent patient‐level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann–Whitney estimator 0.52, 95% confidence interval (CI) 0.45–0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow‐up, patients with left ventricular end‐diastolic volume of 200–370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16–0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09–0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years. Conclusions Longitudinal follow‐up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long‐term clinical follow‐up thus offers guidance for future targeted trials.