AIMS:Anaemia is among the most prevalent comorbidities in heart failure with preserved ejection fraction (HFpEF), but pooled prognostic estimates predate the contemporary left ventricular ejection fraction (LVEF) ≥50% definition and combine legacy with contemporary cohorts. We quantified the association between World Health Organization (WHO)-defined anaemia and all-cause mortality in HFpEF and tested whether it persists under the stricter ejection-fraction threshold. METHODS AND RESULTS:Following PRISMA 2020 (PROSPERO CRD420251361160), we searched five databases from inception to 2026 and included cohort studies reporting an adjusted hazard ratio (aHR) for binary WHO-defined anaemia vs all-cause mortality in an ejection fraction-stratified HFpEF population; every estimate was verified against its primary source and screening was duplicated (κ = 1.00 after adjudication). Of 6123 records, 20 studies were included; 17 (109 909 patients; anaemia prevalence 26%-70%; follow-up 12-72 months) contributed to two pre-specified co-primary pools analysed with Paule-Mandel random-effects models and Hartung-Knapp-Sidik-Jonkman variance correction: a legacy pool (LVEF ≥40%, k = 17) and a contemporary pool (LVEF ≥50%, k = 12). Anaemia was associated with higher all-cause mortality in both: aHR 1.49 (95% CI 1.35-1.66; 95% prediction interval (PI) 1.07-2.09; I2 = 85%) in the ≥40% pool and 1.41 (1.26-1.57; PI 1.06-1.87; I2 = 83%) in the ≥50% pool, both PIs excluding the null. The estimate was stable across 12 pre-specified sensitivity analyses (range 1.45-1.52) with no influential study. Across four Bayesian priors, the posterior median aHR was 1.39-1.49 with posterior probability of harm ≥.999, and a robust Bayesian model-average that entertains null, homogeneity, and publication-bias models returned aHR 1.41 (95% credible interval 1.17-1.58). Although small-study effects were detected (Egger P = .03), the bias-corrected estimate was essentially unchanged (PEESE aHR 1.39). A per-1 g/dL lower-haemoglobin dose-response meta-analysis (k = 6) yielded aHR 1.17 (1.08-1.27). The accrued sample exceeded the diversity-adjusted required information size, and GRADE certainty was moderate under the prognostic-factor framework. CONCLUSIONS:WHO-defined anaemia is independently associated with a ∼40-50% higher all-cause mortality in HFpEF, preserved under the contemporary LVEF ≥50% definition and robust to extensive sensitivity, Bayesian, and bias-correction analyses. These findings support incorporating anaemia into HFpEF risk assessment and motivate mortality-powered trials in rigorously defined HFpEF, while not implying that anaemia correction improves outcomes. REGISTRATION:PROSPERO CRD420251361160.
BACKGROUND:Heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction causes substantial global burden with limited therapies, especially for HFpEF. This pilot study assessed safety and efficacy of a 10-week individualized intermittent hypoxia-hyperoxia exposure (IHHE) program, hypothesizing good tolerability and improvements in exercise capacity and quality of life (QoL). METHODS:In this prospective mechanistic feasibility study, HFpEF and HFrEF patients completed supervised seated IHHE sessions three times weekly for 10 weeks using a medical altitude breathing device (ReOxy, Ai Mediq S.A., Luxembourg). Blood pressure (BP) was monitored before and after sessions. Pre- and post-intervention assessments included echocardiography, cardiopulmonary exercise testing (CPET), 6-minutes walking test (6MWT), isokinetic muscle strength, body composition, biomarkers, patient-reported outcomes, and clinically indicated right heart catheterization (RHC). RESULTS:Nine outpatients (5 HFpEF, 4 HFrEF; age 66.6±10.9 years, 22% female, BMI 27.9±5.4 kg/m2) completed the study. IHHE was safe and well tolerated (adherence 95%), with no adverse events. Across weeks 1-10, post-session reductions in systolic (β =-5.95 mmHg) and diastolic blood pressure (β=-3.74 mmHg), and heart rate (β=-5.18 bpm) were measured (all p< 0.001). A significant decrease of fat mass index 9.32±2.56 vs. 8.92±2.41 kg/m2 (P=0.031), and visceral fat area 127.6±30.6 vs. 121.9±29.7 cm2 (P=0.005), as well as an increase of body mineral content 3.14±0.57 vs. 3.21±0.55 kg (P=0.028), and tissue impedance (RB250: 4.02±0.50 vs. 4.12±0.56 kHz, P=0.041), were measured. There was a numeric improvement (not statistically significant) of peak VO2 1536 [1148; 2064] vs. 1828 [1476; 2175] mL/min (P=0.674, about +300 mL/min), 6MWT 499.66±71.65 vs. 521.12±62.59 m (P=0.260, about +22 m), and right leg peak torque flexion 74±21.77 vs. 81.68±22.67 Nm (P=0.109) and extension 119.89±36.31 vs. 122.69±38.77 Nm (P=0.641). RHC showed no adverse acute hemodynamic effects, while invasively measured left ventricular systolic pressure decreased during hypoxia (151 vs. 120 mmHg). No changes in QoL were observed (P≥0.384). CONCLUSION:Ten-week IHHE was safe and feasible in HF patients and led to improved BP and body composition and showed trends toward better exercise capacity. Larger randomized trials are needed to confirm these results.
BACKGROUND:Right ventricular (RV) dysfunction (RVD) represents a power independent prognostic factor in patients with chronic heart failure (CHF); poor evidence exists about the effect of current guideline directed medical therapy on RVD.We investigated whether dapagliflozin improves right ventricular function, right ventricular-pulmonary arterial coupling and pulmonary artery systolic pressure compared with standard therapy in CHF. METHODS:This is a prospective observational registry with propensity score analysis investigating RV function and right heart failure(RIVED), focused on the effects of Dapagliflozin.Efficacy measures were intra and inter-groups changes from baseline to 6 months in RV end diastolic diameter(RVEDD), tricuspid annular peak systolic excursion(TAPSE), RV global longitudinal strain(RVGLS), fractional area changes(FAC), RV systolic tissue doppler wave(S'), PASP values,TAPSE/PASP,and tricuspid regurgitation(TR).Secondary endpoints were N-terminal pro B-type natriuretic peptide(NTproBNP) levels changes and combined adverse events rate of mortality and hospitalization at 180 days. RESULTS:The final population analysed was of 142 patients,in a balanced dataset consisting of 71 treated with standard HF therapy plus dapagliflozin(Dapa group) and 71 treated with standard therapy without dapagliflozin(control group).Median age was 78 [75-84] years old and 62% of patients were men. Patients in dapa group were younger(76[66-82] vs 82[74-88] years old;p<0.001) and more frequently affected by diabetes mellitus(44% vs 22%; p=0.002) compared to control group. No significant differences were observed between the two groups in terms of gender, renal function, NTproBNP and NYHA class.Over the 6 months follow-up,the Dapa group showed a significant improvement of RV function compared with controls(TAPSE +1.03 mm,p < 0.001 and S' +0.48 cm/s,p = 0.006); whereas no significant differences between-groups were observed for FAC(p = 0.16).RV GLS at follow-up was significantly improved in the Dapagliflozin group compared with controls(adjusted mean difference -1.54%, p < 0.001). as well as of the pulmonary-arterial coupling (TAPSE/PASP adjusted differences ranging from +0.07 to +0.17,p = 0.025).In patients with PH, a significant decrease in PASP(30[25-34] vs 37[31-45] mmHg,p<0.001) associated with a RVGLS significant improvement (-20 [-22 - -19] vs -19 [-20 - -17] p<0.001) in the Dapagliflozin group were observed.TAPSE/PASP ratio was significantly improved in Dapagliflozin group with respect to the control group(0.67[052-0.78] vs 0.51[0.42-0.61], p<0.001).Secondary endpoints analysis revealed that NT-proBNP levels were significantly improved from baseline to follow-up only in dapaglifozin group(from 938 to 726 pg/ml p = 0.013).The rate of 180-days adverse events was significantly higher in control group with respect to Dapaglifozin group(21% vs 8%, p<0.01). CONCLUSIONS:In a real-world HF cohort,dapagliflozin was associated with improved RV morphology and function, lower PASP,and better RV-PA coupling,suggesting a direct haemodynamic and RV-targeted benefit beyond LV remodelling.Trial Registration: (ClinicalTrials.gov Identifier: NCT06002321).
Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.
BACKGROUND:In the C-MIC II trial, C-MIC therapy improved outcomes in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We evaluated whether differences in background HF medication adjustments influenced the observed benefits. METHODS:Ambulatory patients with chronic non-ischemic HFrEF receiving guideline-directed medical therapy (GDMT) were enrolled. The primary outcome was change in GDMT and diuretic intensity over 6 months. Treatment effects on left ventricular ejection fraction (LVEF), Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and 6-minute walk distance (6MWD) were assessed by baseline sodium-glucose cotransporter-2 inhibitor (SGLT2i) use for consistency. RESULTS:Among 65 patients, 25 (39%) had GDMT adjustments (C-MIC device: 44%; control 33%; p= 0.390). GDMT intensity increased in controls (Δ +0.36) but decreased (Δ -0.16; p= 0.100) in C-MIC group. Diuretic intensity decreased in C-MIC group (Δ -0.10) but increased in controls (Δ +0.12; p= 0.200). When stratified by baseline SGLT2i use, C-MIC therapy induced consistent improvements in LVEF (SGLT2i: +6% [95% CI 3-9; p<0.001] vs. without SGLT2i: +4% [95% CI 2-7; p=0.003]), KCCQ-OSS (SGLT2i: +42 points [95% CI 26-58; p<0.001] vs. without SGLT2i: +40 [95% CI 28-51; p<0.001]) and 6MWD (SGLT2i: +150 meters [95% CI 88-212; p<0.001] vs. without SGLT2i: +141 meters (95% CI 63-219; p<0.001]). CONCLUSION:Medication intensity decreased in C-MIC-treated patients but increased in controls, driven primarily by escalation of diuretics, likely reflecting worsening HF. Consistent improvements in LVEF, 6MWD and KCCQ-OSS across SGLT2i subgroups suggest that the observed benefits are independent of background pharmacologic intensification.
Managing cardiorenal syndrome in acute decompensated heart failure remains a major challenge in contemporary cardiology. While pharmacological decongestion with diuretics is the cornerstone of therapy and is effective in most patients, worsening renal function and diuretic resistance continue to pose challenges in selected cases. Device-based therapies are increasingly explored to target key pathophysiological mechanisms underlying cardiorenal dysfunction. This expert review builds on a conceptual framework for device-based therapies. Rather than cataloguing individual technologies, we apply a functional framework that classifies devices according to their primary mode of action: reduction of venous or lymphatic congestion ('pullers'), augmentation of arterial perfusion ('pushers'), and direct removal of sodium and/or fluid ('removers'). For each category, we integrate pathophysiological rationale with available clinical evidence, highlighting the predominance of early-phase physiological evidence and the need for randomized studies demonstrating benefit beyond optimized contemporary medical care.
INTRODUCTION:Chronic heart failure (HF) is associated with mild cognitive impairment (MCI), vascular dementia, and Alzheimer's disease. Blood-based neurodegenerative biomarkers may support early risk stratification and outcome prediction in HF. METHODS:In the prospective Cognition.Matters-HF cohort study, serum neurofilament light chain (NfL), glial fibrillary acidic protein, and phosphorylated tau protein-181, as well as plasma amyloid-β peptides (Aβ38, Aβ40, Aβ42) and β-synuclein, were quantified longitudinally over 36 months using ultrasensitive immunoassays and immunoprecipitation mass spectrometry. Cerebral magnetic resonance imaging and standardized domain-specific cognitive testing were performed. Multivariable logistic regression was used to assess associations with future MCI, brain structural changes, and 5-year all-cause mortality. RESULTS:Among 104 patients with chronic HF (10% female, age 64 ± 10 years), all biomarkers except NfL increased significantly over 3 years (P < .05). Median annual percentage changes were 36.6% for phosphorylated tau protein-181, 4.6% for glial fibrillary acidic protein, 2.6% for β-synuclein, 0.6% for Aβ38, 0.5% for Aβ40, and 0.3% for Aβ42. After adjusting for clinical confounders, increases in Aβ38 and Aβ42 independently associated with future MCI, pathological white matter hyperintensity progression (>5% per year), and 5-year mortality (all P < .05). Glial fibrillary acidic protein levels and phosphorylated tau protein-181 trajectories were independently associated with pathological brain atrophy (>0.3% per year). CONCLUSION:In clinically stable patients with chronic HF, longitudinal increases in circulating amyloid-β peptides associated with cognitive decline, structural brain changes, and mortality. Serial biomarker assessment provided stronger prognostic information than baseline measurements alone. Replication in larger cohorts is required.
AIMS:Acute decompensated heart failure (ADHF) is often treated with diuretic agents in both the inpatient and ambulatory settings, yet fluid overload frequently persists and is associated with rehospitalization and death. In patients with predominant interstitial fluid expansion but without intravascular overload, increasing the loop diuretic dose or adding a second diuretic may cause intravascular volume depletion, electrolyte disturbance, and worsening renal function without clearing the excess tissue fluid. COMPRESSION-HF tests whether adding lower limb compression to standard diuretic treatment improves early decongestion in patients with ADHF, predominant peripheral oedema, and inferior vena cava (IVC) diameter ≤21 mm. METHODS:COMPRESSION-HF (NCT06418932) is an investigator-initiated, multicentre, randomized, double-blind, sham-controlled trial in which adults with ADHF, bilateral leg oedema (grade II or higher of IV), N-terminal pro-B-type natriuretic peptide (NT-proBNP >1000 pg/ml), and IVC diameter ≤21 mm were assigned 1:1 to active bilateral lower limb compression (two-layer inelastic-elastic bandaging; manufacturer-specified nominal ankle pressure, approximately 20 mm Hg) plus parenteral furosemide or to sham bandaging plus parenteral furosemide, for up to 72 h. The two co-primary endpoints are 24-h urinary sodium excretion and change in body weight from baseline. Secondary endpoints include changes in lower limb circumference, clinical congestion score, and IVC diameter, together with NT-proBNP at 72 h, cumulative 72-h furosemide-equivalent dose, carbohydrate antigen 125 (CA-125) at day 15 ± 3, and 30-day safety. Continuous endpoints will be analysed with mixed-effects analysis of covariance or repeated-measures models including centre as a random intercept. Recruitment is complete (106 patients randomized); the trial was powered to detect a 20 mmol between-group difference in 24-h urinary sodium excretion. CONCLUSIONS:COMPRESSION-HF will show whether adding lower limb compression to standard loop diuretic treatment increases natriuresis and weight loss in patients with ADHF and predominant peripheral oedema, and will describe the relationship between tissue congestion, intravascular refilling, and the diuretic response.
BACKGROUND AND AIMS:Type 2 diabetes mellitus (T2DM) and obesity are the archetypal components of cardiometabolic syndromes associated with heart failure (HF) with preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). The specific contribution of T2DM, independent of obesity, to myocardial adaptations and outcomes remains uncertain. We aimed to explore the obesity-independent contribution of T2DM to cardiac structure, function, central haemodynamics, and outcomes. METHODS:We leveraged the sham-control arm of the REDUCE LAP-HF II trial (n = 312), a prospectively phenotyped cohort of patients with HFpEF/HFmrEF undergoing invasive haemodynamic assessment. Multivariable models were used to adjust for body mass index (BMI) and clinical covariates. Outcomes included cardiovascular (CV) death and total HF events. RESULTS:T2DM was present in 37% of patients and was associated with higher BMI, chronic kidney disease, and prior HF hospitalization. Obesity was present in 62% of patients and was more prevalent in those with T2DM (70% vs 57%, P = .032). After adjustment for BMI, T2DM remained independently associated with greater left ventricular mass, lower EF, impaired left ventricular global longitudinal strain, reduced right ventricular free-wall strain, and higher resting filling pressures. Over a median of 4.0-year (2.5-5.0) follow-up, T2DM was independently associated with increased risk of HF events or CV death (adjusted hazard ratio: 1.96, 95% confidence interval: 1.28-3.00), driven by HF events, whereas BMI was not independently prognostic. CONCLUSIONS:HFpEF/HFmrEF patients with T2DM experience adverse myocardial remodelling, impaired biventricular function, adverse central haemodynamics, and worse clinical outcomes independent of obesity. These findings indicate that T2DM confers additional metabolic burden to the myocardium, beyond that attributable to obesity alone.
BACKGROUND:Cognitive impairment (CI) affects a significant percentage of heart failure (HF) patients, reducing adherence and worsening outcomes. Routine cognitive assessment remains limited. OBJECTIVES:To evaluate cognitive assessment practices, identify barriers, and examine associations between knowledge, attitudes, and clinical behaviours among clinicians managing HF patients. METHODS:An anonymous cross-sectional survey was distributed to 120 cardiologists across 68 clinics in the Hellenic Heart Failure Clinics Network (May-June 2025). The 13-question survey examined knowledge on cognitive decline, personal opinions on screening, assessment methods, and implementation obstacles. Associations were examined using Pearson's chi-square. RESULTS:Fifty-one cardiologists completed the survey, corresponding to a response rate of 42.5%. Among respondents 80% reported awareness of the high prevalence of cognitive decline, 14% systematically screened for CI presence. Main barriers reported were lack of time (76%) and inadequate familiarity with assessment tools (50%). Screening frequency was not associated with HF patient volume (χ2 = 4.75, P = .58). Significant correlations were demonstrated between (i) knowledge on CI and frequency of screening (V = 0.37, P = .04); (ii) frequency of screening and support of establishing screening as routine practice (V = 0.50, P < .001); and (iii) frequency of screening and referral of patients to specialists (V = 0.39, P = .007). All respondents expressed interest in further education. CONCLUSION:There is a gap between awareness of and testing for CI in HF patients, with the latter not being affected by clinicians' patient load. Since there is universal interest in learning, integrating screening tools into daily routines and creating clear referral pathways may help in addressing this evidence-practice gap.
AIMS:Despite previous studies investigating the impact of mitral regurgitation (MR) in acute heart failure (AHF) there are inconsistencies in trial data, and no meta-analyses to date. Our aim was to explore if MR is associated with mortality in AHF. METHODS AND RESULTS:We performed a meta-analysis of AHF patients with MR to investigate any association with all-cause mortality. We identified 27 studies that met our inclusion criteria, encompassing 73,363 patients (age 72.9±4.2years; females 44.4%) with an average follow-up of 1.9 years. Moderate/severe MR was associated with an unadjusted 47% increased mortality risk compared to no/mild MR (OR 1.47 [95% CI 1.30-1.66, p<0.001]). This excess risk of death persisted among studies reporting adjusted data (OR 1.21 [95% CI 1.01-1.45, p=0.038]). Compared to those with no MR, MR severity was associated with increasing risk of death: mild MR OR 1.22 [95% CI 0.98-1.53, p=0.079], moderate MR OR 1.48 [95% CI 1.1-2.01, p=0.011] and severe MR OR 1.60 [95% CI 1.13-2.27, p=0.008]. We observed excess mortality in moderate/severe MR compared to no/mild MR among individuals with a left ventricular ejection fraction (LVEF) <50% (OR 1.26 [95% CI 1.18-1.35, p<0.001]) and LVEF 40-50% (OR 2.00 [95% CI 1.59-2.50, p<0.001]) but not LVEF >50% (OR 1.16 [95% CI 0.91-1.47, p=0.23]. Neither meta-regression nor pre-specified sensitivity analyses affected MR's association with the primary outcome. A substantial degree of heterogeneity was observed across the included studies. CONCLUSIONS:We observed that MR during AHF is associated with increased mortality. Although causality cannot be inferred due to the observational design and high heterogeneity of the included studies, MR may represent a phenotype amenable to targeted therapies during decompensated heart failure.
INTRODUCTION:The incidence, risk and resuscitation characteristics of out-of-hospital cardiac arrest (OHCA) in the non-ischaemic dilated cardiomyopathy (NIDCM) population have not been analysed before in an unselected nationwide population, and could provide insight into risk stratification and prevention of sudden cardiac death in this unique heart failure cohort. METHODS:We conducted an observational, register-based study with cohort and nested case-control analyses using Denmark's healthcare registers between 1 June 2001 to 31 December 2022. DCM was classified as non-ischaemic using validated methods combined with exclusion of other causes of ischaemia or abnormal loading conditions. Incidence rates and hazard ratios were calculated in the general population. Absolute risk was determined using the Aalen-Johansen estimator in an exposure-matched cohort including incident NIDCM patients and matched controls. Resuscitation characteristics were determined in a nested case-control study. RESULTS:The incident rate of OHCA was approximately 12 times higher in NIDCM patients compared with the general population (incidence rate 532 vs 45 per 100 000 person years). The 5- and 10-year risk of OHCA for male de novo NIDCM patients was 2% and 3.4%, respectively (vs 0.6% and 1.1% for non-NIDCM) and 1.4% and 2.1% for female de novo NIDCM patients (vs 0.4 and 0.5% for non-NIDCM). NIDCM OHCAs had higher rates of initial shockable rhythm than non-NIDCM OHCAs (48.5% vs 22.3%, P < .001) but no significant differences in 30 day and 1-year mortality (79% vs 84% and 82% vs 84, respectively). CONCLUSIONS:The Danish NIDCM population has a significantly increased incidence of OHCA compared to the general population but a comparable mortality despite multiple positive resuscitation characteristics.
INTRODUCTION:Limited health literacy is common among patients with heart failure (HF), and the relative importance of general and disease-specific health literacy for patient outcomes remains unclear. This study aimed to evaluate general and disease-specific health literacy in patients with HF and to examine their association with behavioural, patient-reported and clinical outcomes. METHODS:This prospective observational study included 126 outpatients with HF (mean age 69 ± 11 years; 71% male) who were followed for 6 months. General health literacy was assessed using the Brief Health Literacy Screen (BHLS), and disease-specific health literacy using the Heart Failure-Specific Health Literacy Scale (HFsHLS). RESULTS:The two measures were moderately positively correlated (Spearman's ρ = 0.49, P < .001), indicating partial overlap. Limited general health literacy (BHLS ≤ 9) was identified in 22% of patients and was associated with lower educational level, more depressive symptoms, higher NT-proBNP levels, and a greater number of prescribed medications (all P < .05). In univariable analyses, both health literacy measures were associated with better HF-related knowledge (P = .004 and .049), higher health-related quality of life (P < .001 and .007), and better self-rated health (P < .001 for both), which was not sustained after multivariable adjustment. Additionally, disease-specific health literacy was associated with self-care behaviours (P = .033), also after multivariable adjustment (P = .026). Neither measure was independently associated with clinical outcomes (death, HF hospitalization, emergency department visit); however, patients with limited general health literacy showed numerically higher event rates and a tendency towards increased risk of clinical outcomes. CONCLUSION:In patients with HF, limited general health literacy was observed in 22% of patients. General and disease-specific health literacy measures were not interchangeable, and only disease-specific health literacy showed an independent association with self-care behaviours. A tendency towards less favourable clinical outcomes was observed among patients with limited general health literacy.
Advanced heart failure represents a significant and expanding clinical challenge, establishing durable mechanical circulatory support as the critical therapeutic pillar, whether utilized as a bridge to transplantation or as a standalone therapy. This expert review provides a contemporary clinical decision framework that supplements existing guidelines by shifting the primary focus towards the pre-operative phase and the essential multidisciplinary processes required for clinical success. This review emphasizes precise patient selection and pre-operative optimization strategies designed to mitigate medical harm. This is particularly important in complex scenarios with relevant cardiac and non-cardiac comorbidities and in early stages of advanced heart failure to adequately address specific high-risk populations and conditions. By codifying the necessity of interdisciplinary team dynamics, targeted ambulatory as well as in-hospital workups, and shared decision-making, this review provides a structured approach to ensure equitable access and optimal long-term survival within the evolving landscape of advanced heart failure care.
BACKGROUND AND AIMS:Heart failure (HF) and chronic kidney disease (CKD) are prevalent and often co-exist. Whether CKD is preferentially associated with a specific HF ejection fraction (EF) phenotype remains unclear. We aimed to investigate the association between CKD and new-onset HF across the EF spectrum and according to CKD severity. METHODS:Patients with a first HF diagnosis from the Swedish HF Registry (2005-2021) were matched 1:1 by sex, year of birth, and county to controls without HF. In separate analyses, CKD was defined according to (i) ICD-10 codes in both HF patients and controls; (ii) an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 in HF patients. Renal function was further stratified into the KDIGO categories G2-G5, i.e. G2:60-89;G3a:45-59; G3b:30-44; G4:15-29; G5 < 15 ml/min/1.73 m2 in eGFR-defined CKD analyses. RESULTS:51 848 HF patients (20% HF with preserved EF [HFpEF], 23% HF with mildly reduced EF [HFmrEF], 57% HF with reduced EF [HFrEF]) and 51 848 controls were considered. CKD was associated with ∼two-fold higher odds of HF, particularly HFpEF, compared with HFmrEF and HFrEF vs non-HF (ICD-10 definition: odds ratio [OR]2.46, 1.30, and 1.52, respectively; P-interaction=0.001) and with 8% higher odds of HFpEF vs HFrEF when defined by eGFR in the HF population. Across KDIGO stages, with G2 as reference, G3b-G5 were more likely associated with HFpEF vs HFrEF, G3a had similar associations with HFpEF and HFrEF, and G3a-G3b were less likely associated with HFmrEF vs. HFrEF. CONCLUSIONS:CKD was independently associated with new-onset HF, especially HFpEF in moderate to advanced CKD, and both HFpEF and HFrEF in mild CKD. Targeting CKD may be crucial to prevent HF.
BACKGROUND:The Charlson comorbidity index (CCI) is a validated weighted measure of comorbidity burden, but has an unclear role in heart failure (HF). OBJECTIVES:To characterize age-adjusted CCI (ACCI) in HF, its association with the use of guideline-directed medical therapy (GDMT) and with outcomes. METHODS:In the Swedish HF registry, patients were divided into 3 groups based on ACCI scores (low 1-3, intermediate 4-6, and high ≥7). We studied its association with clinical characteristics and GDMT use. Multivariable multinominal and Cox regressions were used to analyze ACCI and its association with ejection fraction (EF) category (reduced [HFrEF], mildly reduced [HFmrEF], preserved [HFpEF]), and with outcomes up to 3 years. RESULTS:Among 117,419 patients (age 75 [66-82], 36% women, 53% HFrEF, 24% HFmrEF, 23% HFpEF, median ACCI was 5, 6 and 6 respectively. ACCI ≥7 was present in 31% with HFrEF, 35% with HFmrEF and 42% with HFpEF. A higher ACCI score was associated with higher EF category, NYHA class, serum NT-proBNP, diuretic use, and lower quality of life and GDMT use (p<0.05 for all). The risk of composite CV mortality/first HF hospitalization was higher with intermediate (adjusted HR 1.34, 95% CI 1.29-1.39) and high vs low ACCI (1.76, 1.69-1.83). High ACCI category (vs low) was significantly associated with non-CV (adjusted HR 6.36, 95% CI 5.75-7.04), but also, CV mortality (4.35, 3.99-4.74), and total hospitalizations (adjusted IRR 2.16, 2.11-2.22) but also HF hospitalizations 1.23 (1.17-1.28). CONCLUSION:The ACCI discriminates well in HF, with higher ACCI being associated with greater severity of HF, lesser GDMT use and worse quality of life. Higher ACCI was more strongly associated with death than hospitalization. Higher ACCI was more strongly associated with non-CV outcomes but also with CV and HF outcomes.
BACKGROUND AND AIMS:Severe tricuspid regurgitation (TR) alters ventricular interaction and left-sided filling dynamics. However, the longitudinal effects of transcatheter tricuspid edge-to-edge repair (T-TEER) on left atrial (LA) remodelling and diastolic physiology remain poorly characterized. We aimed to evaluate longitudinal changes in LA structure, function, and diastolic haemodynamics following T-TEER. METHODS:We studied 125 consecutive patients undergoing T-TEER within the TRI-FR trial and registry (median age 78 [73-81] years; 60.8% women; 73.6% atrial fibrillation). Comprehensive echocardiography was performed at baseline, pre-discharge, and at 6 and 12 months. Longitudinal changes in LA volume index (LAVI), peak atrial longitudinal strain (PALS), E/e' ratio, LA stiffness index (LASI), and forward flow indices were analysed using linear mixed-effects models. RESULTS:Left atrial volume index decreased immediately after T-TEER (estimated change -8.1 ml/m2; 95% CI -14.6 to -1.6; adjusted P = .033), but this reverse remodelling was not sustained at 12 months. In contrast, LA reservoir function deteriorated early and remained impaired throughout follow-up [PALS -1.2%; 95% confidence interval (CI) -2.0 to -0.3; adjusted P = .029]. Estimated LV filling pressure increased acutely (E/e' + 3.26; 95% CI 2.34-4.18; adjusted P < .001), while LASI remained elevated at 12 months (ratio 1.22; 95% CI 1.05-1.42; adjusted P = .016). Stroke volume index and cardiac index did not change significantly over time (P = .969 and P = .562, respectively). Early mitral regurgitation worsening occurred in 20% of patients but was transient and unrelated to changes in diastolic or forward-flow parameters. CONCLUSIONS:Transcatheter tricuspid edge-to-edge repair induces immediate anatomical LA unloading but does not restore LA mechanical function. Despite early reductions in LA volume, filling pressure surrogates increased, LA stiffness remained elevated, and forward flow did not improve. These findings demonstrate a dissociation between structural and functional remodelling after TR correction and highlight the importance of serial assessment of LA mechanics and diastolic physiology following T-TEER.
BACKGROUND AND AIMS:Severe tricuspid regurgitation (TR) is associated with increased mortality and hospitalizations for heart failure (HF). Aetiologies of TR include: secondary (atrial or ventricular), primary and cardiac implantable electronic device (CIED)-related. The aim of the study was to assess the prevalence of different TR aetiologies, as well as characteristics and treatment of patients with severe TR in a real-life setting. METHODS:This was a prospective, observational study of patients with severe TR, conducted in 18 cardiology centres. Consecutive adult patients with severe TR were included, regardless of the presence of TR symptoms and the cause of hospital admission. RESULTS:A total of 1295 patients with severe TR were enrolled (median age 76 years, 53% women). The most common reason for admission was HF decompensation (40%). Single TR aetiology was identified in 79% patients. The most frequent overlap between aetiologies included secondary ventricular and atrial TR, and was found in 11% of patients. The most common TR aetiology was secondary atrial (37%), followed by secondary ventricular (25%). Primary and CIED-related TR accounted for 10% and 15%, respectively. In 2.4% TR aetiology was not determined. Patients with secondary atrial and CIED-related TR were the oldest (79 and 78 years, respectively), and those with primary TR the youngest (68 years). Patients with CIED-related and secondary ventricular TR were more often hospitalized for HF decompensation, had more advanced HF symptoms, worse left- and right-ventricular function, worse kidney and liver function, and higher in-hospital mortality. Only 40% of patients underwent evaluation by the Heart Team and 21% were qualified for TR interventions. CONCLUSIONS:In real life, unequivocal identification of TR aetiology remains challenging. Secondary atrial TR is the most common aetiology. There are significant differences in characteristics and outcomes depending on TR aetiology. Too few patients with severe TR undergo evaluation by the Heart Team.
BACKGROUND AND AIMS:Acute decompensated heart failure (ADHF) results in high rates of hospitalisation, re-admissions, and mortality, straining healthcare systems. Loop diuretics are crucial for fluid management in ADHF, but optimal dosing and monitoring remain unclear. The 2021 European Society of Cardiology guidelines suggest individualised dosing based on home diuretic use and close urinary sodium monitoring for better decongestion. This study evaluates the effectiveness of a new natriuresis- and urine output-guided protocol at Maastricht University Medical Centre+ (MUMC+) based on these recommendations. METHODS:This retrospective study compared patients treated with a natriuresis- and urine output-guided protocol, introduced in May 2022, to those receiving standard care before May 2022. The guided protocol involved individualised loop diuretic dosing, regular urine sodium monitoring, and incremental adjustments as needed. Data on demographics, lab values, length of stay, mortality, and re-admission rates were analysed, with statistical adjustments for potential confounders. RESULTS:The guided protocol was associated with significantly shorter hospital stay (median 6.9 vs. 7.5 days, P=0.029), lower six-month mortality (10.9% vs. 17.9%, P=0.017), and cardiac rehospitalisation rates (26.1% vs. 35.7%, P=0.015). These effects were independent of baseline differences and confounders. At 12 months, the guided protocol group showed sustained association of reduced cardiac rehospitalisation rates and a trend toward lower mortality. CONCLUSION:This guided AHF protocol was associated with reduced hospital stays, six-month rehospitalisation rates, and mortality. Tailoring individual optimised diuretic therapy for ADHF seems promising, but further research is needed to confirm its long-term benefits.
