To identify risk factors for atrial fibrillation (AF) progression in adults with congenital heart disease (CHD), a population in which AF is increasingly prevalent yet predictors of progression remain poorly defined. Adults with CHD and AF (N = 125) were followed for 17 ± 8 years. AF progression was defined as transition from paroxysmal to persistent/permanent AF. Coexisting atrial tachycardia, permanent pacing modes, and longitudinal changes in QRS duration (QRSd) and corrected QT interval (QTc) were evaluated. Time-dependent Cox regression and Fine–Gray competing risk models were used to identify risk factors for AF progression. AF progression occurred in 57 (45.6

Abstract Background Tetralogy of Fallot (ToF) accounts for approximately 7 to 10 % of all CHD and is commonly associated with failure of the right ventricle (RV). Parameters providing more insight into the mechanics of RV failure are needed to guide clinical decision making. As advancements in Three-Dimensional (3D) echocardiography (3DE) have enabled more detailed analysis of RV volume and function, the way is paved for new 3D derived parameters. We developed a custom software to assess 3D RV shape and function. Purpose The aim of this study was to evaluate the differences of 3DE derived RV geometry (curvature) and deformation parameters in adults with ToF and controls. Methods In 50 patients with ToF and 50 controls 3DE RV images were acquired. RV geometries from 3D datasets were segmented using commercially available RV analysis software (TomTec 4D-RV function 2.0) and processed using custom software (RV-dynamics) to calculate Curvature, Area Strain (AS) and Longitudinal Strain (LS). Parameters were measured globally and over different segments of the RV (i.e. septal body (SB), inferior free wall (IFW), anterior free wall (AFW), lateral free wall (LFW), apex (Ax), RV inflow tract (RVIT), RV outflow tract (RVOT), anterior boundary (AB) and posterior boundary (PB)). Results Globally and for all independent regions of the RV, AS was significantly reduced in patients with ToF as compared with healthy controls. Except for AFW, global and all regional values of LS were significantly reduced in patients with ToF as compared with healthy controls. Global AS and LS were strongly correlated with RVEF with values for r of -0.9 and -0.6 respectively. RV curvature differed over multiple segments, predominantly in the end-diastolic Ax and end-systolic PB and Ax regions. Conclusion The RV-dynamics software gives the opportunity to analyze 3D RV morphology and RV deformation parameters in the diseased RV in more detail. AS and LS may provide more detailed assessment of the functional condition of the diseased RV in ToF whereas curvature provides an interesting method for the quantification of RV remodeling. Further insight in the different mechanisms of dysfunction of the RV may improve clinical decision making.

Background Congenital aortic stenosis (ConAoS) accounts for approximately 4%–8% of all congenital heart diseases. Chronic pressure overload may result in myocardial stiffening, leading to impaired cardiac filling, reduced contractility and ultimately contributing to the onset of symptomatic heart failure. Shear wave elastography (SWE), using high-frame-rate echocardiography, allows visualisation of myocardial shear waves. By measuring shear wave propagation velocity (SWV), this technique may enable non-invasive assessment of myocardial stiffness. This study aimed to explore the feasibility of SWE in adults with ConAoS and to compare SWV with healthy volunteers (HVs).Methods In 68 adult patients with ConAoS—including 17 patients after aortic valve replacement (AVR)—and 19 HVs, high-frame-rate recordings were acquired in the parasternal long-axis view. Custom software was used to measure SWV by manually placing M-mode lines through the interventricular septum after aortic valve closure.Results SWE feasibility was 73% in ConAoS patients with a native aortic valve (NV), 53% post-AVR and 100% in HVs. Median SWV was 4.7 m/s (3.2–5.5) in NV patients, 3.7 m/s (3.1–5.4) post-AVR and 3.4 m/s (3.0–4.4) in HVs (p=0.200). Patients with moderate-to-severe ConAoS demonstrated higher SWV compared with HVs (4.7 m/s (3.4–5.6) vs 3.4 m/s (3.0–4.4); p=0.035).Conclusions SWE is feasible in the majority of ConAoS patients. Higher SWV in moderate-to-severe ConAoS patients, despite preserved diastolic function in most cases, may reflect early myocardial mechanical alterations and provide a promising non-invasive marker for myocardial stiffening. Further technical optimisation and cross-platform validation are essential for clinical translation.

Aims:Tetralogy of Fallot (ToF) is a congenital heart disease requiring surgical repair in early childhood. Affected patients cope with severe right ventricle (RV)-related morbidity during adulthood, which is mostly attributed to RV remodelling. Improved understanding of RV remodelling patterns is essential for advancements in clinical decision-making and treatment planning. Consequently, a method to enable detailed quantification of directional components of RV function was developed using 3D echocardiography (3DE). Methods and results:From RV-focused 3DE studies of 50 ToF patients and 50 healthy controls, 3D dynamic RV meshes were obtained using commercially available software (TomTec 4D RV-Function). A software tool was developed in-house to decompose RV contraction in longitudinal (LT), radial, and anteroposterior (AP) motion directions. Their respective contributions to RV ejection fraction (EF) were calculated. The AP contraction component was identified as the main contributor in RV function deterioration, showing significant relative reduction in ToF patients compared with healthy controls [38% (31-42) vs. 40% (37-44), P = 0.004]. Conversely, the LT direction showed significant relative increase in ToF compared with healthy controls [28% (26-33) vs. 26% (23-31), P = 0.009]. Conclusion:Our custom software allowed for effective directional decomposition of RV EF, enabling detailed quantification of RV function in patients with ToF. RV function deterioration was primarily due to a decreased contribution of AP wall motion to RV EF, whereas LT contribution showed relative increase. These findings highlight the need for more detailed RV function assessment for improved understanding of RV remodelling.

Background Atrial arrhythmias are common after tetralogy of Fallot (TOF) repair but rare following ventricular septal defect (VSD) repair. While postoperative factors may contribute, preoperative electrophysiological differences could also underlie this different arrhythmia risk. Objective To compare preoperative atrial electrophysiology between pediatric patients with TOF and VSD. Methods Intraoperative epicardial mapping was performed in the atria (right atrium (RA), left atrium (LA), pulmonary vein (PV) and Bachmann’s Bundle (BB)) of 26 TOF and 41 VSD children. Potential voltage and morphology, as well as conduction properties were analyzed. Results Despite a lower prevalence of LA dilatation in TOF patients than VSD patients (29% vs 81%, p = 0.004), TOF exhibited lower potential voltages in the LA and PV (LA: 3.4±1.7mV vs 5.3±2.5mV; PV: 1.8 (1.1, 5.6)mV vs 4.7 (1.4, 8.9) mV, both p<0.01) with more low-voltage areas (LA: 12.9 (0.0, 53.7)% vs 4.4 (0.0, 29.0)%; PV: 23.9 (3.6, 47.0)% vs 7.0 (0.0, 35.9)%, both p<0.01), a higher prevalence of conduction block (LA: 0.6 (0.0, 6.5)% vs 0.0 (0.0, 1.2)%, p<0.001) and potentials containing 2 deflections (short double potentials (LA: 12.1 (0.5, 41.8)% vs 8.8 (1.3, 18.9)%, p=0.032); long double potentials (LA: 0.1 (0.0, 13.8)% vs 0.0 (0.0, 2.2)%, p=0.034)). Conclusion Pediatric TOF patients have particularly at the LA and PV more atrial electrophysiological abnormalities than VSD patients, suggesting that atrial electrophysiological alterations at these sites are more pronounced in TOF patients.

Background:Right ventricular (RV) function is crucial in the prognosis of adults with congenital heart disease (ACHD). However, its relationship with exercise capacity (EC) and quality of life (QoL) in ACHD remains underexplored. Despite the established benefits of physical activity in CHD, there is limited knowledge regarding the cardiac effects of exercise training in ACHD. Aim:To assess the relationship between RV function, comprehensively evaluated using two-dimensional multiplane echocardiography (2D MPE), and both EC and QoL in adults with various types of CHD. Additionally, to investigate the effect of a 16-week home-based aerobic and strength exercise program on these parameters. Methods:Fifty-five ACHD underwent transthoracic echocardiographic assessment of RV function, including conventional parameters and longitudinal RV strain, both measured from four RV walls using 2D MPE. The patients also completed a cardiopulmonary exercise test and a QoL questionnaire, and were randomized to either conventional care or a 16-week home-based rehabilitation program combining aerobic interval cycle training and dynamic strength exercises, followed by retesting. Results:At baseline, RV function correlated with EC, measured by percent-predicted peak oxygen consumption. Moreover, significant correlations were observed between RV and QoL parameters, including physical functioning, general health perception and visual analogue scale score. EC, muscle strength and QoL improved following the exercise program, while 39% of patients in the intervention group were non-adherent. Conclusion:RV function correlates with EC and QoL in a diverse ACHD population. ACHD patients should be encouraged to engage in regular exercise, and exercise training should be integrated into CHD treatment.

BACKGROUND:Left ventricular (LV) remodeling is becoming increasingly important in assessing the impact of aortic stenosis (AS). However, data on structural LV remodeling in congenital AS patients is scarce. Therefore, this study aimed to describe LV remodeling before and after aortic valve replacement (AVR) in adults with congenital AS and identify markers associated with myocardial fibrosis. METHODS AND RESULTS:In this prospective study, adult patients with congenital AS were included with 1) at least mild AS (Vmax ≥2.5 m/s) or 2) prior AVR due to congenital AS. Cardiovascular Magnetic Resonance (CMR) was performed to assess structural LV remodeling. Results were compared with CMR data from 20 healthy controls. Data from 73 patients were included (median age 43 [30-52] years, 67% male), of whom 20 patients were post-AVR. LV systolic function was preserved in all patients. LV mass index was significantly higher in patients with a native valve than in controls (70 ± 19 vs. 59 ± 8 g/m2, p = 0.023). Late gadolinium enhancement (LGE) was present in 19 patients (26%): 13 with a native valve and 6 post-AVR (25% vs. 30%, p = 0.64). Native T1 and extracellular volume (ECV) did not differ significantly from healthy controls. In patients post-AVR, LV mass index and matrix volume were significantly lower compared to patients with a native valve. CONCLUSION:LGE was present in a quarter of adults with congenital AS. However, ECV in patients with native valves did not differ significantly from healthy controls. LV dimensions were lower in patients post-AVR, but LGE persisted, indicating LV remodeling even after AVR.

Background Patients with adult congenital heart disease (ACHD) frequently develop late complications despite early surgical repair, including ventricular dysfunction and arrhythmias. In conditions with predominant right-sided pathology such as atrial septal defect (ASD), pulmonary stenosis (PS) and Tetralogy of Fallot (ToF), leading to right ventricular dilatation or systolic/diastolic dysfunction, ventricular interdependence may result in impaired left ventricular filling and left atrial (LA) dysfunction, despite the absence of primary left-sided disease. LA strain (LAS) has demonstrated prognostic value in acquired heart disease but its role in ACHD remains incompletely defined.Objective To evaluate the prognostic significance of LAS in adults with repaired right-sided CHD.Methods This single-centre longitudinal study includes patients with ACHD such as ASD, PS and ToF from the Quality of Life study at the Erasmus Medical Center. All patients underwent surgical repair during childhood between 1968 and 1980. Detailed cardiological evaluation, including STE-derived assessment of LA reservoir (LASr), conduit and contractile (LASct) function, was performed in 2012. Clinical outcomes were collected over a 10-year follow-up period, including mortality, reinterventions, heart failure and symptomatic tachyarrhythmias (supraventricular or ventricular) requiring treatment.Results A total of 195 patients were included (ASD=78 (40%); PS=45 (23%); ToF=72 (37%)), with a mean age of 40.7±5.2 years at the time of evaluation. Patients with ToF exhibited more frequent interventricular conduction abnormalities at baseline and had 2.7-fold higher odds of reaching the composite endpoint compared with patients with ASD. In Cox regression analyses, LASr and LASct were independently associated with symptomatic tachyarrhythmias (LASr: HR=0.952, p=0.013; LASct: HR=0.936, p=0.046), and these associations remained significant after adjustment for left ventricular ejection fraction, LA volume index or N-terminal pro B-type natriuretic peptide.Conclusion LAS provides independent prognostic information after surgical repair of right-sided CHD, particularly for predicting symptomatic tachyarrhythmias. Impaired LA deformation identifies patients at increased risk, underscoring the clinical relevance of LA mechanics in ACHD follow-up.

Tetralogy of Fallot (ToF) accounts for approximately 7–10

Aims:To compare transthoracic echocardiography (TTE), 2D and 4D flow cardiovascular magnetic resonance (CMR) for the evaluation of valve function and flow measurements after percutaneous pulmonary valve implantation (PPVI). Methods and results:In this multicentre exploratory observational study, 29 patients who underwent PPVI were planned for TTE and CMR with 2D and 4D flow measurements after PPVI. Peak velocity was measured with all techniques. Net and regurgitating flow measurements were measured with CMR distal to the transcatheter pulmonary valve (TPV). Median peak velocity of the TPV with TTE was 2.5 (2.0-3.1) m/s, with 2D flow CMR 2.3 (2.0-3.2) m/s, and with 4D flow 2.3 (2.0-3.0) m/s. There was a good correlation for the peak velocity of the TPV between TTE and 2D flow CMR (r = 0.68, P < 0.001) and a moderate correlation for peak velocity between TTE and 4D flow CMR (r = 0.56, P = 0.003), and between 2D flow and 4D flow CMR (r = 0.56, P = 0.006). For peak velocity measurements, no proportional bias was observed between the three imaging techniques. For the CMR flow measurements, a strong correlation was observed between 2D and 4D flow CMR, for both net flow (r = 0.87, P < 0.001) and regurgitation fraction (r = 0.96, P < 0.001) of the TPV. Net flow through the left pulmonary artery correlated strongly between 2D and 4D flow CMR (r = 0.85, P < 0.001), and there was a good correlation for the right pulmonary artery (r = 0.65, P < 0.01). For net flow measurements of the TPV, we found an underestimation of flow measurements at higher flow rates with 4D flow CMR, compared to 2D flow CMR. Conclusion:TTE, 2D flow CMR, and 4D flow CMR are all feasible and reliable imaging techniques after PPVI, concordant in predominantly mild-to-moderate stenosis. These findings strengthen the use of 2D and 4D flow CMR as a tool for post-PPVI assessment, despite stent-induced artefacts, although reliability in more advanced valve dysfunction remains uncertain.

Background: The prognostic value of electrocardiography (ECG)- and continuous rhythm monitoring (CRM)-derived markers for predicting atrial fibrillation (AF) onset and progression remains unclear in patients with congenital heart disease (CHD). Methods: We retrospectively analyzed 573 CHD patients who underwent 24 h Holter monitoring between 2003 and 2015. Baseline ECG and CRM parameters were assessed. Cox regression identified predictors of new-onset AF and AF progression, and interaction analyses explored effect modification by left atrial (LA) dilatation. Results: During 13 ± 5 years of follow-up, AF occurred in 107 patients (18.7%), of whom 32 (29.9%) progressed to persistent/permanent AF (PeAF). Patients with AF more frequently had prolonged PR and QTc intervals and higher atrial ectopy (AE) and ventricular ectopy burdens. Independent predictors of new-onset AF were older age, LA dilatation, higher AE burden, atrial tachycardia, and pacemaker implantation. AF progression was independently associated with older age, LA dilatation, higher AE burden, and prolonged PR interval. AE burden showed a stronger association with AF risk in patients without LA dilatation. Conclusions: In CHD patients, baseline ECG PR-intervals and CRM-derived AE burden independently predict AF onset and/or progression. These noninvasive markers may improve risk stratification and support earlier personalized rhythm management.

Background Atrial septal defect (ASD) is associated with an increased risk of atrial fibrillation, traditionally attributed to chronic right atrial (RA) volume overload. However, the contribution of aging, independent of volume overload, to RA remodeling is unclear. Objective To determine the role of aging in RA electrical remodeling in unrepaired ASD patients without atrial tachyarrhythmias. Methods High-resolution epicardial RA mapping was performed in 72 ASD patients (34 pediatric, 38 adult) before surgical correction. Potential morphology, low-voltage areas (LVA), and conduction block (CB) were quantified. Associations between age and electrophysiological properties were assessed using linear regression models adjusted for clinical covariates. To isolate the effect of age, an additional generalized estimating equation analysis was conducted in an age-matched cohort of 45 non-ASD controls. Results In ASD patients, age was independently associated with higher LVA burden (β[95% CI] per 10 years: 1.4% [0.7–2.0]; P<0.001), long-double potentials (LDP; 0.9%, [0.2–1.5]; P=0.008), and CB (0.5% [0.2–0.8]; P=0.001) in fully adjusted model. These age-related associations were region-specific, mainly involving LVA in superior RA, LDP in inferior RA, and CB in RA free wall. Age-related associations persisted in control cohort, supporting an effect independent of ASD-related volume overload (fully adjusted model: LVA: 1.3% [0.5–2.1]; LDP: 1.3% [0.5–2.0]; CB: 0.7% [0.4–0.9]; P<0.001, respectively). Conclusions Aging is an independent contributor to RA electrical remodeling in unrepaired ASD patients. These findings highlight the role of age as a substrate modifier, independent from volume overload, may guide arrhythmia risk stratification in this population.

BACKGROUND:Non-invasive assessment of arrhythmogenic substrates underlying persistent atrial fibrillation (AF) could potentially provide patient-tailored ablation therapy. Speckle Tracking Echocardiography (STE) is an imaging modality, which can be used to assess atrial biomechanical function. As biomechanical dysfunction is driven by electrical dysfunction, STE may serve as a diagnostic tool to detect AF-related arrhythmogenic substrates. PURPOSE:To investigate which non-invasive STE-derived measurements correlate best with invasively determined electrophysiological properties as a first step towards developing a novel, non-invasive diagnostic tool. METHODS:Intraoperative epicardial mapping during sinus rhythm was performed in adult patients (n = 19, mean age: 63 ± 13 years) undergoing cardiac surgery. Potential voltages, potential morphology, conduction velocity (CV), conduction block (CB: ≥12 ms) and uninterrupted lines of conduction delay (CD: ≥7 ms) and CB (CDCB) were quantified. Atrial end-diastolic reservoir and contractile strain values were used to calculate area under the curve, and the slopes of both the reservoir and contractile phases. RESULTS:Steeper LA reservoir strain slopes were associated with more CDCB, greater CV variation and lower overall CV around the pulmonary veins (ρ = 0.55, p < 0.001; ρ = 0.64, p = 0.004; ρ = -0.55, p = 0.019). A larger right atrial volume indexed correlated with more CDCB, fractionated potentials and reduced CV on Bachmann's Bundle (ρ = 0.64, p = 0.008; ρ = 0.52, p = 0.037; ρ = -0.61, p = 0.011). Right atrial end-systolic time strongly correlated with CB, low-voltage area's and fractionated potentials on Bachmann's Bundle (ρ = 0.68, p < 0.001; ρ = -0.63, p = 0.009; ρ = 0.53, p = 0.020). CONCLUSION:STE timing and slope parameters correlated most strongly with atrial electrophysiological properties, supporting their potential as non-invasive markers for arrhythmogenic substrates and patient-tailored ablation therapy.

OBJECTIVES:Acute type A aortic dissection (ATAAD) carries high mortality, with emergency surgery being the cornerstone of treatment. The German Registry for Acute Type A Aortic Dissection (GERAADA)-score is advocated in guidelines to predict 30-day mortality after ATAAD surgery. This study investigates its performance in a Dutch cohort, with an emphasis on malperfusion definitions, age groups, and sex. METHODS:Adults undergoing emergency surgery for ATAAD at 5 Dutch centres (2007-2024) were included in a multicentre database. External validation of the GERAADA-score was performed with these data, using discrimination (area under the curve [AUC]) and calibration (Brier score, Hosmer-Lemeshow test, and calibration plots). A logistic regression with GERAADA variables was fitted on the study population, and assumptions were checked. Subgroup analyses were conducted based on sex, age groups, and malperfusion definitions (including imaging and clinical definitions). RESULTS:A total of 1,146 patients underwent emergency surgery for ATAAD. Observed early mortality was 16.9% (n = 194). Of 1,130 patients included in the external validation cohort, 92.2% had low-intermediate risk (GERAADA-score ≤ 30%). The GERAADA-score showed moderate discrimination (AUC = 0.649, 95% confidence interval = 0.604-0.694), with a higher AUC for younger patients (50-59 years). The malperfusion definition including ischaemia confirmed by imaging showed the best discriminative power. Calibration was good (Hosmer-Lemeshow, P = .754, Brier score = 0.131). Logistic regression identified age, catecholamine use, ventilation support, and coronary and peripheral malperfusion as independent risk factors for 30-day mortality, with signs of multicollinearity between preoperative catecholamine use and resuscitation. CONCLUSIONS:In the Dutch setting, the GERAADA-score demonstrated moderate discriminative power and good calibration across relevant subgroups. Adaptations of the GERAADA-score, including conducting a haemodynamic instability variable, may be considered to avoid redundant predictions and boost reproducibility.

Pulmonary arterial hypertension (PAH) is a life-threatening disease of the pulmonary arteries. Progressively increasing pulmonary artery pressure may lead to fatal failure of the right ventricle, necessitating aggressive drug treatment. Sotatercept, a novel drug for PAH-targeted therapy, shows promising results in clinical trials. Nevertheless, efficacy in the heterogeneous PAH population and long-term outcomes have yet to be investigated. This case report illustrates the life-changing effects of sotatercept in a patient with heritable PAH associated with a TBX4 mutation. Our patient faced near immobility, oxygen dependency, and was listed for lung transplantation in November 2023. Following sotatercept administration from July 2024 onward, she started sporting activities and has been removed from the transplantation waiting list. Thereby, this case illustrates an exceptional response to sotatercept in a patient with TBX4-associated heritable PAH. Positive effects persist 1 year after initiation without significant side effects.

Background Atrial septal defect (ASD) is associated with severe right atrial dilatation, which may contribute to the arrhythmogenic substrate underlying paroxysmal atrial fibrillation (PAF). However, detailed characterization of electrical properties has not been systemically performed in these patients with PAF. Objectives The purpose of this study was to explore differences in the prevalence of potential fractionation and low-voltage areas between uncorrected adult ASD patients with PAF and control patients, to elucidate predilection sites underlying PAF in ASD patients. Methods Epicardial sinus rhythm mapping of the right atrium and left atrium (LA) and Bachmann's bundle was performed during cardiac surgery. Sixteen adult ASD patients with PAF (ASD-PAF group) were matched with 16 ASD patients without AF (ASD-No-AF group) and 16 patients without congenital heart disease but with PAF (control group). Unipolar potentials were classified as single potentials, short double potentials, long double potentials, or fractionated potentials (FPs). Potentials with amplitudes <1.0 mV were labeled as low voltage areas (LVAs). Results A total of 48 patients (age: 57 ± 11 years, 64.6% men) were included. FPs were more frequently observed in the ASD-PAF group than in the ASD-No-AF group or control group, either in the entire atrium (4.6% [Q1-Q3: 3.3%-5.1%] vs 1.9% [Q1-Q3: 1.4%-3.1%] and 2.3% [Q1-Q3: 1.1%-3.3%]; P < 0.05 for all) or in the LA (4.3% [Q1-Q3: 2.5%-10.6%] vs 2.0% [Q1-Q3: 1.1%-2.6%]; P = 0.017 and 1.7% [Q1-Q3: 0.6%-3.6%]; P = 0.066). Furthermore, not at the right atrium, but only at the LA was the amount of LVA greater in ASD-PAF group (11.2% [Q1-Q3: 8.6%-19.4%] vs 4.1% [Q1-Q3: 2.6%-6.3%] and 3.9% [Q1-Q3: 2.0%-8.2%]; P < 0.05 for all). Conclusions Electrical properties in uncorrected adult ASD patients with PAF are characterized by significantly more FP and LVA compared with control patients with PAF or ASD patients without PAF. Importantly, these differences in conduction abnormalities are restricted to the LA, supporting the role of the LA in the pathophysiology of PAF in right-sided heart congenital heart disease.

BACKGROUND:Red blood cell distribution width (RDW), a routine and inexpensive blood parameter, is widely available and may serve as a useful screening marker for heart failure (HF). This study aims to evaluate RDW's predictive value for new-onset HF in the general population and examine its incremental predictive performance alongside NT-proBNP. METHODS:From a prospective population-based cohort, RDW and NT-proBNP were available for 5814 and 3393 individuals without prior HF, respectively. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Fully adjusted model included variables from the Pooled Cohort Equations (PCE): age, sex, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking, and antihypertensive medication use. Predictive improvement was assessed using the Δc-statistic. RESULTS:Over a median follow-up of 7 years, 433 individuals developed HF (incidence rate: 10.4 per 1000 person-years). Each 1% increase in RDW was associated with a 22% higher HF risk (HR 1.22, 95%CI, 1.12-1.32), and those in the highest RDW quartile had a 71% higher risk (HR 1.71, 95%CI, 1.29-2.25). NT-proBNP showed similar associations (HR 1.68, 95%CI, 1.40-2.01 per 1-unit increase). Adding RDW to the PCE model significantly improved predictive performance (Δc-statistic = 0.008), comparable to NT-proBNP (Δc-statistic = 0.014). CONCLUSIONS:RDW is a robust and accessible predictor of incident HF. Its predictive value, low costs, and routine availability highlight its potential as a useful biomarker for HF risk stratification in the general population. The design and findings are summarized in the graphical abstract.

BACKGROUND:By combining left ventricular (LV) global longitudinal strain (GLS) with LV volume during the cardiac cycle, LV strain-volume loops (SV-loops) can be generated. LV SV-loop derived parameters provide new insights into the interaction between cardiac contraction and volume in a variety of cardiac diseases and may even have prognostic value. The aim of this study is to describe SV-loops in a healthy adult population and investigate potential sex- and age-related differences of LV SV-loop characteristics. METHODS:In 125 healthy volunteers aged 18-72 years, apical 2-, 3- and 4-chamber views were acquired to measure GLS. Custom software was used to combine strain and volume data to construct SV-loops. Different parameters were derived: (i) linear slope of systolic strain-volume relation (S-Slope); (ii) linear slope of early-systolic strain-volume relation (ES-Slope); (iii) linear slope of early-diastolic strain-volume relation (ED-Slope); (iv) linear slope of late-diastolic strain-volume relation (LD-slope) and (v) uncoupling between systolic and diastolic strain-volume relation (UNCOUP). RESULTS:For systolic strain-volume relation, higher values were observed in females compared to males, with S-Slope values of 0.19 %/mL m-2 [0.17-0.22] and 0.13 %/mL m-2 [0.11-0.14], respectively (p < 0.001). Similarly, ED-Slope was higher in females than in males, with values of 0.18 %/mL m-2 [0.10-0.28] and 0.12 %/mL m-2 [0.06-0.18] respectively (p = 0.003). Low values for uncoupling between the systolic and diastolic strain-volume relation were observed, with a mean value of 0.34 ± 1.1. Additionally, UNCOUP was positively correlated with age (r = 0.4; p < 0.05). CONCLUSIONS:Higher values observed in systolic and early-diastolic strain-volume relation in females may reflect sex-specific differences in LV contraction. While the exact mechanisms remain unclear, these findings suggest potential variations in myocardial deformation patterns that warrant further investigation. Consistent with previous work, relative coupling of the systolic and diastolic strain-volume relationship was identified in our cohort of healthy individuals. However, with increasing age, higher values for uncoupling were observed, suggesting age-related alterations in ventricular mechanics that may contribute to changes in cardiac function over time.