During exercise, vascular resistance, the ratio of arterial pressure to blood flow [i.e., cardiac output (CO)], is an important component of the hemodynamic response determining peak oxygen uptake (V̇o2peak). However, how systolic blood pressure (SBP) responses reflect this pressure-flow relationship, and their association with V̇o2peak remain incompletely understood. We performed cardiopulmonary exercise testing in 135 females (51 ± 8 yr) across a broad fitness spectrum to evaluate V̇o2peak and SBP responses. SBP responses were stratified by maximal SBP (SBPmax <190 mmHg or ≥190 mmHg) and workload-indexed SBP (SBP/W-slope; low vs. high based on sex- and age-specific median values). Peak CO (COpeak) was quantified from exercise cardiac magnetic resonance imaging. SBPmax ≥190 mmHg occurred in 74 participants (55%), high SBP/W-slope in 41 (30%), and 26 (19%) had both. A high SBP/W-slope was associated with lower V̇o2peak (1.7 ± 0.4 vs. 2.1 ± 0.6 L/min; P < 0.001) and COpeak (12.8 ± 2.3 vs. 15.7 ± 3.5 L/min; P < 0.001) and higher total peripheral resistance (TPRpeak; 11.2 ± 2.3 vs. 9.0 ± 2.0 mmHg·min/L; P < 0.001). In contrast, a low SBP/W-slope despite SBPmax ≥190 mmHg had the highest V̇o2peak and COpeak and larger reductions in TPR compared with high SBP/W-slope groups. SBPmax ≥190 mmHg in isolation was associated with higher V̇o2peak and COpeak, although it also identified females with low fitness and COpeak. Thus, SBP/W-slope provides a framework for interpreting SBP relative to flow, with higher slopes indicating an unfavorable pressure-flow profile characterized by higher vascular resistance, lower COpeak, and reduced V̇o2peak. In contrast, SBPmax reflects both flow and resistance. Incorporating SBP/W-slope may therefore improve identification of females with impaired pressure-flow regulation.NEW & NOTEWORTHY In females, a higher workload-indexed systolic blood pressure (SBP/W)-slope during exercise was associated with greater peripheral vascular resistance, lower cardiac output, and lower cardiorespiratory fitness, irrespective of maximal systolic blood pressure (SBPmax). In contrast, an exaggerated SBPmax alone reflected differing contributions of increased flow (i.e., cardiac output) or increased vascular resistance across individuals. Evaluating the SBP/W-slope provides a more physiologically informed interpretation of exercise blood pressure and may improve identification of females with impaired pressure-flow regulation and reduced cardiovascular reserve.

INTRODUCTION:Remodelling of the left atrium (LA) and left ventricle (LV) occurs in response to pathological and physiological stimuli, yet their inter-dependence is often overlooked in clinical practice. The left atrioventricular ratio (LA:LV)-the ratio of maximal LA end-systolic volume (LAESV) to LV end-diastolic volume (LVEDV)-may offer valuable context for distinguishing physiological from pathological cardiac remodelling. METHODS AND RESULTS:This study evaluated LA:LV, assessed via echocardiography, and cardiorespiratory fitness assessed as peak oxygen uptake (VO2peak) in a multi-centre international cohort spanning the cardiorespiratory fitness spectrum. Exercise capacity in healthy participants was categorized by VO2 peak quartiles, and cardiac structural differences were analysed. Among 2943 adults (1600 healthy, 1343 pathology), healthy individuals had a median LA:LV of 0.49 [0.38, 0.61], consistent with LVEDV being roughly twice the LAESV. Pathology revealed higher LA:LV ratios [0.53 (0.38-0.75), P < 0.001], with marked elevations amongst AF [0.60 (0.45-0.78)] and HFpEF [0.70 (0.51-0.88)]-a 30% increase vs. healthy adults. The highest indexed LA volumes occurred in the highest VO₂ peak quartile [Q4: 36 (28-46) mL/m²], while the LA:LV ratio was highest in Q1 [0.53 (0.42-0.69)]. Among participants with elevated LAVi (≥34 mL/m²), concordance with elevated LA:LV ratio (≥0.75) varied markedly by fitness level: ∼60% in Q1-Q2 vs. only 7% in Q4, highlighting the importance of fitness context when interpreting LA enlargement. CONCLUSION:The LA:LV ratio effectively discriminates between adaptive and maladaptive atrial remodelling. LA:LV is typically ∼0.5. Lower ratios correlate with higher functional capacity and physiological remodelling, whereas ratios ≥0.75 may indicate pathological remodelling and warrant consideration of atrial pathology.

Aims:To define rates of diagnostic image acquisition, clinical drivers of image quality and the learning curve for artificial intelligence (AI)-guided image acquisition on point-of-care ultrasound (AI-POCUS) in rural and remote communities. Methods and results:AI-guided image acquisition on point-of-care ultrasound was performed using AI software integrated with a desktop ultrasound system in 181 participants (65 ± 15 years, 47% female). A standardized training protocol included online material, lab attendance for 1 day, and online mentoring. Diagnostic-quality images were obtained from 72% of parasternal and 55% of apical images (P < 0.001). Scans were classified as 'Diagnostic' if diagnostic-quality images were obtained in the majority of parasternal and apical views (ACEP score ≥3) in ≥50% of windows for both apical and parasternal views. Body surface area (BSA) [OR 0.16 (0.05;0.50), P = 0.002] and hypertension [OR 0.50 (0.27;0.93), P = 0.03] were associated with diagnostic image quality in the apical window, whereas only hypertension [OR 0.43 (0.20;0.88), P = 0.024] was associated with diagnostic quality in the parasternal window. The learning curve was assessed by comparing the quality according to quantity of scans performed and professional background (nurse, health worker, or general physician). Physician-acquired scans [OR 3.85 (1.92;8.33), P < 0.001], scan 11th onwards [OR 2.86 (1.45;5.56), P = 0.002], and users who performed ≥20 scans [OR 3.58 (1.79;7.14), P < 0.001] predicted study completeness. Conclusion:In rural community practice, the learning curve associated with AI-POCUS diagnostic quality seems longer than reported in other studies from inpatient settings. In novice users, diagnostic quality is greater in the parasternal than the apical windows.

INTRODUCTION:Haptically enabled robotic teleoperated echocardiography (HERTEC) could improve access to skilled sonographers for patients in rural and remote areas. We sought to determine the feasibility, measurement accuracy, and participant responses to the performance of a robotic echocardiogram performed by a sonographer at a distance. METHODS:In this cross-sectional study, 41 asymptomatic adults without known cardiac disease underwent focused echocardiography studies using a handheld ultrasound (HHU) device and robot. This device employed a collaborative robotic arm, force-torque sensors, and remote haptic control. Image quality was assessed using the 5-point American College of Emergency Physicians (ACEP) scale from 1 (no recognizable structures) to 5 (excellent quality fully supporting diagnosis). A 5-point Likert scale questionnaire assessing participant feedback on safety was obtained posttest. RESULTS:American College of Emergency Physicians scores of the HERTEC system indicated 95% adequate quality (≥3) for parasternal long-axis, 91% for aortic valve-level parasternal short-axis, and 93% for apical 4-chamber views but lower rates for apical 2- and 3-chamber views (71%), with significant differences across windows. All HHU images reached adequate quality for each view. Structural measures demonstrated minor differences between robotic and HHU for left ventricular diastolic dimension (HHU 4.6 vs HERTEC 4.4 cm, P < .001) and left ventricular mass (HHU 126 vs HERTEC 115 g, P = .002). Quality scores were significantly different between methods for the mitral valve short-axis (P = .008), papillary muscle (P = .008), apical 2-chamber (P < .001), and apical long-axis (P < .001) views. The time to complete the study was the most significant difference between the HHU and HERTEC (5.2 ± 1.8 vs 25.2 ± 8.1 minutes, P < .001). Participants felt safe and informed and were willing to repeat robotic scans, with confidence in control features and diagnostic ability. Compared to traditional ultrasounds, 16% were less comfortable with robotic pressure and 10% expressed less overall comfort with the procedure. CONCLUSIONS:HERTEC consistently produced lower-quality images than a standard HHU but achieved echocardiography measurements comparable to HHU in most views, with excellent participant safety perceptions and high acceptability despite minor comfort differences. These findings indicate that robotic teleoperated heart ultrasound may have future potential, but technical advances to improve image quality and speed are required before clinical application.

Cardiac filling is constrained by a reduced ejection time and diastolic period as heart rate increases during exercise. We compared cardiac filling dynamics in endurance athletes and controls during exercise to determine how athletic status influences hemodynamic constraints during exercise. Thirty-two participants (21 endurance athletes and 11 controls) underwent exercise echocardiography at 20, 40, and 60% of peak power output. We measured cardiac timing, stroke volume (SV), and flow rates (SV indexed to body surface area and phase duration). Data were analyzed using linear mixed models. Athletes demonstrated resting bradycardia (44 ± 8 vs. 68 ± 14 beats/min, P < 0.001), through an extended ejection time (296 ± 38 vs. 247 ± 30 ms, P < 0.001) and diastolic filling (811 ± 229 vs. 560 ± 161 ms, P = 0.005). Preexercise cardiac outputs were matched (P = 0.969). During exercise, there was a significant group × exercise interaction for left ventricular (LV) ejection time (P < 0.001) and diastolic period (P < 0.001), indicating distinct athletic adaptations. Although the systolic-to-diastolic (S/D) ratio was similar at rest, a significant interaction occurred during exercise (P = 0.013). Athletes also achieved a greater cardiac output response (group × exercise interaction: P < 0.001). Indexed stroke volume increased similarly in both groups (interaction: P = 0.271) yet remained significantly higher in athletes (group effect: P < 0.001). Consequently, athletes maintained superior absolute volumes throughout the protocol, resulting in greater high-intensity stroke volumes. Athletes are able to produce greater reductions in both LV ejection and diastolic filling time and generate higher stroke volumes during exercise, permitting greater cardiac outputs and a greater exercise response.NEW & NOTEWORTHY This study reveals that endurance athletes' slow resting heart rates provide additional time for ventricular filling. During intense exercise, athletes compensate for dramatically shortened filling times by achieving remarkably higher flow rates, particularly during systole. These differences allow athletes to maintain larger stroke volumes at both rest and at high heart rates, producing superior cardiac outputs and highlighting a key physiological mechanism underlying endurance performance.

OBJECTIVES:Swimming-induced pulmonary oedema (SIPE) is a potentially fatal condition associated with open-water swims. We sought to quantify the contribution of cardiac dysfunction to SIPE. DESIGN:We aimed to assess the incidence of SIPE during an endurance cold water swim. We determined associations between SIPE and changes in cardiac function through a SIPE questionnaire, lung ultrasound (LUS), cardiac biomarkers (N-Terminal pro-B-type natriuretic peptide (NT proBNP) and cardiac troponin I (cTnI)) and transthoracic echocardiograms (TTE). METHODS:Twenty open-water swimmers (10 males) underwent a TTE, LUS for pulmonary oedema and cardiac biomarkers before, 2-hours and 24-hours after an 8-hour swim. Swimmers had an additional LUS and rated their breathlessness upon leaving the water. Participants with breathlessness and 3 or more B-lines present in two or more LUS views were considered SIPE positive. RESULTS:Five swimmers (25 % of cohort) presenting with post-event breathlessness and evidence of lung water were considered SIPE positive. SIPE had no demonstrable effect on left systolic function (LV ejection fraction, global longitudinal strain [GLS]), diastolic function (left atrial volume, E/e') and right ventricular (RV) function (RV fractional area change and RV free wall GLS). SIPE was associated with a small increase in troponin post-swim (at 2 hours SIPE+ 32.1 ng/L, SIPE- 12.6 ng/L, p = 0.004: at 24 hours SIPE+ 12.6 ng/L, SIPE- 4.8 ng/L, p = 0.04) but had no impact on NT proBNP. CONCLUSIONS:SIPE is common in open-water swimmers following an endurance swim and is identified using LUS. Whilst SIPE was associated with a small increase in post-swim troponin levels, no further evidence of cardiac dysfunction was identified at two hours after the swim to explain the pulmonary oedema.

BACKGROUND:Adult cancer survivors are at increased risk of heart failure (HF) due to standard risk factors and cancer treatment-related cardiac dysfunction. However, the prevalence and treatment of subclinical/stage B heart failure (SBHF) in this population are not well defined. OBJECTIVES:The REDEEM (Risk-guided Disease managEment plan to prevEnt heart failure in patients treated with previous cardiotoxic cancer treatMents) trial will evaluate HF screening and targeted intervention in long-term cancer survivors. METHODS:Survivors ≥40 years old, ≥5 years post potentially-cardiotoxic therapy, and with ≥1 HF risk factor were screened by echocardiography for SBHF (abnormal global longitudinal shortening [GLS], left ventricular hypertrophy [LVH], diastolic dysfunction or abnormal 3-dimensional left ventricular ejection fraction [3D-LVEF]). Those with SBHF were randomized to multidisciplinary cardio-oncology disease management plan (CO-DMP), including neurohormonal blockade, exercise training and risk factor optimization, or usual care. The primary endpoint is change in cardiorespiratory fitness (VO2peak) over 6 months. RESULTS:Of 1,124 survivors screened, 604 underwent echocardiography, and 145 (24%) had SBHF (age 68±18 years; 81% women). Of those eligible for randomization, 64% had breast cancer and 35% had hematological malignancy. Although baseline 3D-LVEF was preserved (52.8 ± 6.8%), subclinical LV dysfunction was common (GLS 15.6 ± 2.1%) and 39% had evidence of functional impairment (VO2peak≤18ml/kg/min-1). Abnormal GLS was associated with age, BMI, diabetes and anthracycline exposure, whereas functional impairment was only associated with age. Abnormal GLS and functional impairment were not significantly associated (OR 0.90 [95% CI 0.72-1.11], P = .360). CONCLUSIONS:Risk-based screening can identify a high-risk subpopulation of cancer survivors with SBHF. REGISTRATION:ClinicalTrials.gov NCT04962711, https://www. CLINICALTRIALS:gov/study/NCT04962711.

Screening for HF may identify asymptomatic abnormalities of LV structure or function, described as stage B heart failure (SBHF) in asymptomatic patients with type 2 diabetes mellitus (T2DM). Sodium-glucose transport protein-2 (SGLT2) inhibitors are associated with reduction of overt HF in T2DM, but the mechanism of their effect in SBHF remains obscure. We sought to assess the response of cardiac function and exercise capacity to dapagliflozin vs placebo in T2DM with stage B HF. The LEAVE-DM (Limiting the progression of Echocardiographically-Assessed left VEntricular dysfunction in Diabetes Mellitus) trial assessed echocardiography and 6-min walk (6MWD) in 262 people with well-controlled T2DM (age 73 ± 7 years; 159 women). Those with LVD (n = 139) were randomized 1:1 to dapagliflozin 10 mg/day or placebo. Follow-up was undertaken at 6 and 24 months and the primary endpoint was global longitudinal strain (GLS). Within the randomized group with LV dysfunction, dapagliflozin was associated with reduction of LA volume index (− 2.0 ± 9.0 vs. 0.03 ± 8.6, p = 0.002), and average E/e′ (− 0.1 ± 2.4 vs. 0.7 ± 2.4, p < 0.001), and improved LA reservoir strain (1.8 ± 4.0 vs. − 0.2 ± 4.0, p = 0.02) from baseline to 6 months follow-up. There was an improvement in exercise capacity on dapagliflozin at 6 months follow-up (Δ6MWD 17 ± 46 vs. 2 ± 73 m, p = 0.001). However, although abnormal GLS (< 16 https://www.anzctr.org.au/ ).

Remodelling of the left atrium (LA) and left ventricle (LV) occurs in response to both pathological and physiological stimuli, yet their interdependence is underutilised in clinical practice. While LA and LV volumes are typically assessed independently, the left atrioventricular ratio (LA/LV) may offer valuable context in distinguishing physiological from pathological cardiac changes. To understand the relationship between CRF and LA/LV. This study evaluated the relationship between LA/LV, assessed via echocardiography, and cardiorespiratory fitness (CRF) in a multi-centre international cohort. The study was designed to encompass the upper and lower ends of the CRF spectrum, including patients referred for exertional dyspnoea and competitive endurance athletes, as well as ostensibly healthy controls. Patients with an LV ejection fraction <50%, as well as those with ischaemic heart disease, congenital heart disease, valvular heart disease of moderate or greater severity, sustained cardiac arrhythmias or pulmonary disease of moderate or greater severity were excluded. CRF was quantified by maximal cardiopulmonary exercise testing and participants were stratified into quartiles of peak oxygen uptake (VO2peak) and cardiac structural differences between CRF quartiles were analysed. The cohort (n=1698, mean age 56±19 years, 53% female) had a mean LA/LV ratio of 0.53±0.21. The highest indexed LA volumes were observed in the highest CRF quartile (Q4, 29±12mL/m²). However, the LA/LV ratio decreased with increasing CRF quartiles (Q1: 0.62 ± 0.30; Q4: 0.48 ± 0.14, p<0.001), suggesting that individuals with the highest CRF had the largest LA volumes but the lowest LA/LV ratios. Among those with enlarged LA volume (LAVi ≥ 34mL/m²), the prevalence of LA/LV above 0.75 was 75% in Q1, 67% in Q2, 35% in Q3 but only 4% in Q4. The LA/LV ratio is a novel metric that contextualises LA remodelling, offering a nuanced understanding of physiological versus pathological enlargement. In individuals with LA enlargement, the LA/LV ratio provides a valuable marker of functional tolerance, with potential clinical utility in differentiating adaptive remodelling from disease states. Figure 1: Schematic representation of the relationship between LA/LV and exercise capacity, categorised into quartiles of cardiorespiratory fitness (CRF). Values are n (%) or mean ± SD. LAVi = indexed left atrial volume.

Background Familial dilated cardiomyopathy (DCM) is characterized by marked variability in phenotypic penetrance. The extent to which this is determined by patient‐specific environmental factors is unknown. Methods and Results A retrospective longitudinal cohort study was performed in families with DCM‐causing genetic variants. Environmental factors were classified into 2 subsets based on evidence for a causal link to depressed myocardial contractility, termed (1) DCM‐promoting factors and (2) heart failure comorbidities. These factors were correlated with DCM diagnosis and disease trajectory after accounting for relevant confounders and familial relatedness. A total of 105 probands and family members were recruited: 51 genotype positive, phenotype positive, 24 genotype positive, phenotype negative, and 30 genotype negative, phenotype negative. Demographic characteristics were similar between the 3 genotype groups. DCM‐promoting environmental factors (eg, alcohol excess) were enriched in genotype‐positive, phenotype‐positive individuals compared with genotype‐positive, phenotype‐negative (P<0.001) and genotype‐negative, phenotype‐negative (P=0.003) individuals and were significantly associated with age at DCM onset (hazard ratio, 2.01; P=0.014). Heart failure comorbidities (eg, diabetes) had a similar prevalence in genotype‐positive, phenotype‐positive and genotype‐negative, phenotype‐negative individuals but were significantly reduced in the genotype‐positive, phenotype‐negative group. Fluctuations in left ventricular ejection fraction during follow‐up were linked to changes in environmental factors in 35 of 45 (78%) of instances: 32 (91%) of these were DCM‐promoting factors. Conclusions We identified distinct subsets of environmental factors that affect DCM penetrance and trajectory. Our data highlight DCM‐promoting environmental factors as key determinants of penetrance and natural history. Collectively, these findings provide a new framework for risk factor assessment in familial DCM and have important implications for clinical management.

Echocardiography is the gateway to appropriate therapy for many cardiovascular diseases, but access to this test is sometimes challenging. The consequence is that patients in rural and remote areas need to travel for testing, and the resulting time and monetary costs may prove a barrier, especially for hospital inpatients. Delays in obtaining echocardiograms lead to delayed diagnosis and treatment. Technological advances in miniaturization and processing power, and reductions in cost, have enabled diagnostic images to be obtained from inexpensive echocardiography machines. However, imaging by nonexperts is difficult, even with guidance by artificial intelligence. An alternative strategy is to use high-bandwidth, low-latency communication systems to bring the expertise of an expert sonographer to a remote patient by using a robot. Previous work has shown that remote robots are able to reproduce the hand movements performed by sonographers, and multiple types of robot-guided ultrasound examinations have been performed successfully in remote areas. However, despite clear clinical need and ongoing interest, the promise of robotic tele-echocardiography awaits clinical translation. Existing research points toward longer examination times and a need for additional personnel for local supervision of remotely acquired echocardiograms. The efficiencies of longer examinations and more personnel may be worthwhile to facilitate remote access, or within a hospital to avoid sonographer injury, or to improve safety from infection or radiation exposure during structural heart disease interventions. Potentially, autonomous robot-assisted ultrasound may replace the sonographer, by interfacing with artificial intelligence-guided acquisition, although this remains futuristic and uncertain. This paper reviews recent developments in controlling the speed and force of a recently developed robotic system, means of facilitating positioning of the probe, and haptic control. It emphasizes the primary concerns to be imaging time and safety.

BACKGROUND:Access to echocardiography in remote and rural areas is limited due to a shortage of trained sonographers and the difficulties of accessing isolated regions. A Haptically-Enabled Robot for Teleoperated Echocardiography (HERTEC) was developed to address these disparities, enabling experienced echocardiographers to perform cardiac ultrasound examinations remotely using a robotic platform with integrated haptic feedback. OBJECTIVES:This pilot study evaluated the feasibility of the HERTEC system under varying network latency conditions and feedback settings and assessed ergonomic modifications to the haptic control device. METHODS:Five experienced echocardiographers conducted remote examinations on a healthy volunteer, acquiring five standard cardiac views under three network latency conditions (50 ms, 150 ms, and 250 ms) with haptic feedback enabled or disabled. The haptic device, modified with a dummy probe designed to replicate the feel and orientation of an actual ultrasound probe for improved ergonomics, was tested with and without these changes for analysis. Quantitative metrics, including task completion times, were combined with Likert-scale and open-ended feedback. RESULTS:Enabling haptic feedback reduced acquisition times for some and improved confidence in probe positioning, though its utility varied among users. Network latency above 200 ms noticeably impeded teleoperation performance but did not prevent the acquisition of diagnostic-quality images. The ergonomic modifications received a median comfort rating of 7/10 and an ease of use rating of 8/10, though some noted arm strain requiring further refinements. CONCLUSION:The HERTEC system demonstrates the potential for enabling reliable and efficient remote echocardiography, even under moderate network latency conditions. Haptic feedback and ergonomic enhancements play critical roles in improving usability and operator performance. Future research will focus on refining the system's force-feedback calibration, enhancing ergonomics, and validating clinical efficacy with a larger participant cohort.

Background: Cardiac impairment has been associated with acute COVID-19 since the earliest reports of the pandemic. However, its role in postacute sequelae of COVID-19 ("long COVID") is undefined, and many existing observations about cardiovascular involvement in postacute sequelae of COVID-19 are uncontrolled. Objective: To compare the prevalence of cardiac dysfunction in patients with long COVID and noninfected controls from the same community and explore their association with functional capacity. Methods: Echocardiography was used to assess cardiac structure and function, including the measurement of global longitudinal strain (GLS), in 190 participants with long COVID. All underwent assessment of functional impairment by subjective (Duke Activity Status Index) and objective tests (6-minute walk test). The 190 participants from the long COVID group were matched with those from 979 patients who underwent the same tests in the pre-COVID-19 era, using a propensity score. Results: The 190 patients with long COVID had similar age and risk factor profiles to those of their matched controls. Left ventricular dimensions and geometry, but not diastolic parameters, were significantly altered in the long COVID group. The long COVID group had subclinical systolic dysfunction (GLS 18.5% +/- 2.6% vs 19.3% +/- 2.7%, P = .005), and more long COVID patients had abnormal (<16%) GLS (13% vs 8%, P = .035). The association of long COVID with abnormal GLS (odds ratio, 1.49 [1.04, 2.45]) was independent of-and had a similar or greater effect size than-age and risk factors. There was no interaction of long COVID with the association of risk factors with GLS. As expected, the long COVID group had significant subjective (<85% predicted METS; 72% vs 5%, P < .001) and objective functional impairment (29% vs 24%, P = .026), but GLS was only weakly associated with both subjective (r = 0.30, P = .005) and objective (r = 0.21, P = .05) functional impairment. The presence of long COVID was independently associated with subjective (odds ratio = 159.7 [95% CI, 61.6-414.2]) and objective functional impairment (odds ratio = 2.8 [95% CI, 1.5-5.2]). Conclusions: Impaired GLS and left ventricular dimensions are the echocardiographic features that are overrepresented in long COVID, and this association is similar to and independent of other risk factors. Impaired GLS is weakly associated with functional impairment.

BACKGROUND:The location of the left ventricular outflow tract (LVOT) for measurement of Doppler LVOT stroke volume (SV) remains contentious. Current guidelines recommend LVOT measures at or within 5 mm to 10 mm of the aortic annulus. We aimed to determine the Doppler LVOT SV location that most closely agreed with gold standard cardiac magnetic resonance imaging (CMR). METHOD:This was a retrospective, single-centre, observational study of volunteer participants free of known cardiac disease, using both athlete and nonathlete controls. Participants had their Doppler LVOT SV measured using the area at the annulus, 3 mm, 6 mm, and 9 mm away from the annulus. This was compared to the gold standard CMR SV. RESULTS:Overall, 181 participants had their Doppler LVOT SV measured by echocardiography and CMR, under baseline resting condition. In this population free of cardiac disease, the LVOT area increased progressively from 0 mm to 9 mm from the annulus (4.4, 4.9, 5.7, and 6.95 cm2). The SV obtained at 3 mm from the annulus most closely agreed with CMR. The mean bias and upper and lower limits of agreement of CMR SV vs Doppler LVOT SV were: at 0 mm (11%, -17.78 to 39.76); 3 mm (0.40% -36.78 to 37.58); 6 mm (-16.48%, -72.16 to 39.19); and 9 mm (-43.16%, -114.93 to 28.61). CONCLUSIONS:In patients free of known cardiac disease, measures of LVOT SV within 10 mm of the annulus are not equivalent. LVOT area and SV at 3 mm most closely approximates gold standard CMR SV. LVOT area at the annulus and 6 mm away are within 17% of the CMR SV. The LVOT is larger at 9 mm in this cohort, resulting in a significant overestimation of LV SV.

Background Familial dilated cardiomyopathy (DCM) is characterized by marked variability in phenotypic penetrance. The extent to which this is determined by patient-specific environmental factors is unknown. Methods A retrospective longitudinal cohort study was performed in families with DCM-causing genetic variants. Environmental factors were classified into two subsets based on evidence for a causal link to depressed myocardial contractility, termed (1) DCM-promoting factors and (2) heart failure (HF) comorbidities. These factors were correlated with DCM diagnosis, disease trajectory, and adverse events. Results 105 probands and family members were recruited: 51 genotype-positive, phenotype-positive (G+P+), 24 genotype-positive, phenotype-negative (G+P-), and 30 genotype-negative, phenotype-negative (G-P-). Baseline characteristics were similar between the 3 genotype groups. DCM-promoting environmental factors (eg. alcohol excess) were enriched in G+P+ individuals compared to G+P- (P<0.001) and G-P- (P=0.003) and were significantly associated with age at DCM onset (HR 2.01, P=0.014). HF comorbidities (eg. Diabetes) had a similar prevalence in G+P+ and G-P- but were significantly reduced in the G+P- group. Fluctuations in left ventricular ejection fraction during follow-up were linked to changes in environmental factors in 35/45 (78%) of instances: 32 (91%) of these were DCM-promoting factors. HF comorbidities, but not DCM-promoting factors, were associated with adverse events in G+ individuals (OR 4.9, P=0.004). Conclusion We identified distinct subsets of environmental factors that affect DCM penetrance and adverse outcomes respectively. Our data highlight DCM-promoting environmental factors as key determinants of penetrance and disease trajectory. Collectively, these findings provide a new framework for risk factor assessment in familial DCM and have important implications for clinical management. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Dr. Peters is supported by a Commonwealth Research Training Program Scholarship from the University of Melbourne and the Margaret Henderson Research Fellowship Grant awarded by Melbourne Health. Prof. Kalman is funded by a Practitioner Fellowship of the National Health and Medical Research Council of Australia (NHMRC). Prof. Marwick is funded by an Investigator Grant of the NHMRC. Dr. Fatkin receives support from the Victor Chang Cardiac Research Institute, Heart Foundation, Medical Research Futures Fund, NSW Health, NHMRC, Perpetual Philanthropy and Estate of the Late RT Hall, Australia. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Protocols were approved by the Melbourne Health ethics review board (HREC/18/MH/117). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable Data can be made available by the authors upon reasonable request.

Left atrial (LA) structure better predicts cardiorespiratory fitness (CRF) than LA function. LA function adds little statistical value to predictive models of peak oxygen uptake (V̇o2peak) in healthy individuals, suggesting limited discriminatory for CRF once LA size is factored. In the wider population of ostensibly healthy individuals, the association between increased LA volume and higher CRF provides an important counter to the association between atrial enlargement and heart failure symptoms in those with cardiac pathology.

BACKGROUND Clinical and echocardiographic features predict incident heart failure (HF), but the optimal strategy for combining them is unclear. OBJECTIVES This study sought to define an effective means of using echocardiography in HF risk evaluation. METHODS The same clinical and echocardiographic evaluation was obtained in 2 groups with HF risk factors: a training group (n 1/4 926, followed to 7 years) and a validation group (n 1/4 355, followed to 10 years). Clinical risk was categorized as low, intermediate, and high using 4 -year ARIC (Atherosclerosis Risk In Communities) HF risk score cutpoints of 9% and 33%. A risk stratification algorithm based on clinical risk and echocardiographic markers of stage B HF (SBHF) (abnormal global longitudinal strain [GLS], diastolic dysfunction, or left ventricular hypertrophy) was developed using a classification and regression tree analysis and was validated. RESULTS HF developed in 12% of the training group, including 9%, 18%, and 73% of low-, intermediate-, and high -risk patients. HF occurred in 8.6% of stage A HF and 19.4% of SBHF (P < 0.001), but stage A HF with clinical risk of $9% had similar outcome to SBHF. Abnormal GLS (HR: 2.92 [95% CI: 1.95-4.37]; P < 0.001) was the strongest independent predictor of HF. Normal GLS and diastolic function reclassified 61% of the intermediate -risk group into the low -risk group (HF incidence: 12%). In the validation group, 11% developed HF over 4.5 years; 4%, 17%, and 39% of low-, intermediate-, and high -risk groups. Similar results were obtained after exclusion of patients with known coronary artery disease. The echocardiographic parameters also provided significant incremental value to the ARIC score in predicting new HF admission (C -statistic: 0.78 [95% CI: 0.71-0.84] vs 0.83 [95% CI: 0.77-0.88]; P 1/4 0.027). CONCLUSIONS Clinical risk assessment is adequate to classify low and high HF risk. Echocardiographic evaluation reclassifies 61% of intermediate -risk patients. (c) 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.