Lara-Breitinger, Kyla M

Abstract Background Lipomatous atrial septal hypertrophy (LASH) is generally viewed as a benign anatomical finding. Although extracardiac fat depots have been linked to adverse cardiometabolic outcomes, the prognostic implications of LASH have not been well defined. Purpose To evaluate whether LASH thickness is independently associated with long-term all-cause mortality. Methods We reviewed adult patients who underwent diagnostic transesophageal echocardiography at our Clinic sites from 2010–2017. LASH was identified by a dumbbell-shaped interatrial septum with maximal thickening ≥5 mm in the bicaval midesophageal view. All-cause mortality through January 1, 2024, served as the primary endpoint. Septal thickness was evaluated using restricted cubic splines and Cox proportional hazards models adjusted for age, sex, body mass index, Charlson Comorbidity Index, and left ventricular ejection fraction. Results Among 1,397 patients (mean age 69±12 years; 60% male), median LASH thickness was 14.2±4.4 mm. LASH severity was classified as mild (<15 mm; n=763), moderate (15-20 mm; n=522), or severe (>20 mm; n=112). During 7.5±4.0 years of follow-up, 586 deaths (42%) occurred. Mortality was higher with increasing septal thickness (37%, 46%, and 56%; p < 0.001). Each 1-mm increase in LASH-thickness was associated with higher adjusted mortality (adjusted-hazard-ratio 1.03; 95%-confidence-interval 1.01-1.05). Spline modeling suggested a risk increase beginning near 16 mm; thickness >16 mm carried a 26% higher mortality risk (adjusted-hazard-ratio 1.26; 95%-confidence-interval 1.06-1.50). Conclusions LASH was associated with long-term mortality independent of BMI and other clinical factors. Septal fat accumulation may provide a useful, noninvasive marker that complements broader cardiac risk assessment.Risk for all-cause mortality across LASHFor image description, please refer to the figure legend and surrounding text.

Abstract Background Atherosclerotic cardiovascular disease (ASCVD) develops over a prolonged latent period, progressing from subclinical ASCVD to major cardiovascular events due to plaque accumulation. Subclinical ASCVD is a valid subrogate to assess potential risk factors or ASCVD. Dietary patterns are known to contribute to or prevent ASCVD. Dairy consumption has been associated with lower rates of obesity, hypertension, and diabetes, while saturated fats, present in most dairy products, have been associated with ASCVD. Studies assessing the association between subclinical ASCVD and dairy consumption have shown mixed results but have not been systematically analyzed Purpose This study aimed to systematically review and synthesize the existing evidence on the association between dairy product consumption and subclinical ASCVD Methods The study protocol was registered in the International Prospective Register of Systematic Reviews and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We conducted a comprehensive search of PubMed, EMBASE, Scopus, Cochrane Central Register, Google Scholar, and Web of Science to identify experimental and observational studies that examined the association of dairy product consumption with measures of subclinical ASCVD assessed through coronary artery calcium (CAC) scanning, intima-media thickness (IMT), pulse pressure (PP) or pulse wave velocity (PWV), from inception to July 9, 2024. Titles and abstracts were screened in duplicate, followed by a full-text review and data abstraction from articles that met the study criteria. Dairy products were classified as: a) Dairy, according to the United States Department of Agriculture, encompassing milk, yogurt, cheese, lactose-free milk, and fortified soy milk/yogurt; and b) Dairy+, which further included higher fat content products such as cream cheese, sour cream, cream, and butter Results A total of 973 articles were identified; 22 met inclusion criteria representing 20 studies; being predominantly cross-sectional (55%) conducted in North America (50%); food frequency questionnaires were the most implemented tool for dietary assessment (86%), and 41% used PWV for subclinical ASCVD assessment; Fig. 1. Total Dairy and Dairy+ exhibited predominantly neutral effects with a trend toward a beneficial effect, similar to yogurt intake. Milk and cheese demonstrated contrasting effects, with studies reporting protective, neutral, and harmful associations, particularly for PWV and IMT. Limited data on CAC suggested no strong relationship with dairy consumption; Table 1 Conclusion Available evidence on the association between dairy consumption and subclinical ASCVD is complex with mixed effects across dairy products. No consistent evidence of harm or benefit was found; future research is needed to clarify the role of different dairy components in the development of subclinical ASCVD and incidence of cardiovascular eventsFig1.Summary of studies characteristics Table 1.Summary of effects

Background: Tricuspid regurgitation (TR) is associated with significant morbidity, but individualized treatment and timing of intervention are yet to be defined. We previously proposed and validated artificial intelligence electrocardiography (AI-ECG) scores for various diseases. Whether incorporating AI-ECG information adds to risk stratification above and beyond classical clinical parameters is unknown. Objectives: To identify AI-ECG scores independently associated with all-cause mortality in chronic TR and to create a composite AI-ECG risk score. Methods: Patients with a first echocardiographic diagnosis of ≥moderate TR between 2005-2016 and an ECG within ±15 days were included. The Tricuspid Regurgitation Impact on Outcome (TRIO) score was calculated as previously described based on 8 simple parameters (age, sex, severe TR, heart failure, lung disease, heart rate, creatinine and AST). AI-ECG probabilities of low ejection fraction, aortic stenosis, amyloid, cirrhosis, atrial fibrillation and hypertrophic cardiomyopathy were estimated by existing algorithms; the first 4 were associated with all-cause mortality and a composite AI-ECG risk score was calculated (0-4; 1 point for each AI-ECG above specific threshold). Results: A total of 12,377 pts were included (age 72±13 yrs, 55% women). Over a median follow-up of 1.3 yrs (IQR 0.1 to 4.4), 7,121 pts (58%) died. Mortality risk increased significantly with higher composite AI-ECG risk score (Fig. 1A). On multivariable analysis (proportional hazards method), the composite AI-ECG risk score remained independently associated with death, even after adjusting for age, sex, high NT-proBNP levels (>2,500 pg/mL), right ventricular systolic pressure (RVSP), diuretic use and TRIO risk score category (Fig. 1B). Conclusions: Patients with ≥moderate TR show progressively worse survival with increasing composite AI-ECG risk score. Incorporating AI-derived information from a simple and inexpensive ECG may identify patients with the highest risk of mortality beyond clinical risk scores as TRIO or classical clinical, laboratory and echocardiographic parameters. Prospective validation of this approach needs to be tested in future trials.

Importance Cardiovascular (CV) disease is the leading cause of death globally for both men and women, yet women remain historically underrepresented in CV clinical trials, despite facing a disproportionately high burden of morbidity and mortality in many forms of CV disease. Objective To determine the representation of women across a broad range of CV trials. Evidence Review The participation of women in CV trials registered on ClinicalTrials.gov from 2017 to 2023 was systematically determined through the extraction of publicly available information. Data were extracted to identify the country of study, disease type, trial size, clinical intervention, and age of the participants. The proportion of women and the ratio of number of female to male participants (F:M ratio) were calculated for each trial. The women’s participation:prevalence ratio (PPR) was estimated for each trial based on the relative prevalence of the disease by sex in the specified region. Findings A total of 1079 registered CV trials were identified, including 1 396 104 participants, of whom 571 641 (41.0%) were women. The F:M ratio was significantly lower for studies on arrhythmia (median [IQR], 0.5), coronary heart disease (median [IQR], 0.39 [0.33-0.70]), acute coronary syndrome (median [IQR], 0.32 [0.24-0.51]), and heart failure (median [IQR], 0.51 [0.32-0.87]) but higher for obesity (median [IQR], 1.44 [1.08-4.50]) and pulmonary hypertension (median [IQR], 2.86 [1.50-3.97]) trials. The F:M ratio was higher for trials on lifestyle interventions (median [IQR], 1.51 [0.77-3.24]) than for drug trials. PPRs were low for clinical trials on coronary heart disease (median [IQR], 0.66 [0.50-0.86]), acute coronary syndrome (median [IQR], 0.79 [0.51-0.87]), and stroke (median [IQR], 0.74 [0.61-0.95]). Representation of women in CV trials varied by disease state, region, intervention, and sponsor type. Conclusions and Relevance These findings highlight both progress and persistent challenges in representation of women within CV trials. These gaps not only limit the generalizability of trial outcomes but also perpetuate inequities in evidence-based care for women with CV conditions.

Abstract Aims Tricuspid valve regurgitation (TR) is common and associated with increased mortality. The interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) and association with outcomes is incompletely understood. The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the pulmonary vascular load that the RV must overcome to eject blood. Whether PA Ea discriminates mortality risk in unselected patients with significant TR is unknown. Methods and results In consecutive patients with ≥moderate TR, we compared all-cause mortality at 5 years based on the PA Ea (defined as the RV systolic pressure/stroke volume as measured by transthoracic echocardiography). In a total of 12 682 patients, the median PA Ea was 0.7 mm Hg/mL (interquartile range 0.5, 0.9). Increasing levels of PA Ea were associated with heart failure, liver and kidney disease, and clinical markers of risk such as the Tricuspid Regurgitation Impact on Outcomes score. Increasing levels of PA Ea were associated with larger RVs, worse RV systolic function, higher N-terminal pro-brain natriuretic peptide levels, and greater degrees of right heart failure. After adjusting for age and sex, PA Ea was associated with higher risk of death (hazard ratio 1.55 per 0.5 mm Hg/mL change of PA Ea; 95% confidence intervals 1.51–1.60; P < 0.0001). In multivariable modelling incorporating available clinical variables, PA Ea was independently predictive of outcome compared with other indexes of RV–PA coupling. Conclusion In patients with significant TR, higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify risk.

Abstract Background/Introduction Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) in patients with TR and to investigate their association with outcomes. Various echo parameters have emerged that assess RV-PA coupling, including the ratio of TAPSE to RV systolic pressure (RVSP) and the PA pulsatility index (PAPi). The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the measure of the pulmonary vascular load that the RV must overcome to eject blood into the PA. PA Ea is simple to estimate by echo and found to be an independent haemodynamic risk measure in various left heart and pulmonary hypertension (PH) diseases. Whether PA Ea discriminates risk in unselected patients with significant TR and how it compares to other measures of RV-PA coupling is untested. Purpose To ascertain the prognostic value of PA Ea in patients with TR. Methods In consecutive patients with a first diagnosis of ≥ moderate TR (regardless of aetiology), we compared all-cause mortality at five years based on the PA Ea (defined as the RVSP/stroke volume as measured by transthoracic echocardiography). As stroke volume was measured by Doppler at the left ventricular (LV) outflow tract, patients with > moderate aortic valve regurgitation were excluded. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score was calculated as previously described. PA Ea was separated into 4 groups for comparison based on the separation of quartiles of PA Ea rounded to one decimal place. Results In the 13,608 patients studied, PA Ea could be calculated in 12,682 patients (94.4%). The median PA Ea was 0.68 mmHg/mL (IQR 0.50, 0.92). Increasing levels of PA Ea were associated with clinical comorbidities including heart failure, liver and kidney disease and clinical markers of risk such as the TRIO score. Increasing levels of PA Ea were also associated with larger RVs, worse RV systolic function, higher NT-pro BNP levels, and greater degrees of right heart failure (Table). Each quartile of PA Ea was associated with a significant increase in all-cause mortality (Figure). After adjusting for age and sex, PA Ea was associated with higher risk of death (HR 2.41 (2.28-2.56); p<.0001). While worsening degrees of PA Ea correlated with both declining levels of TAPSE/PASP and PAPi (Table), PA Ea was independently predictive of outcome in a combined model: PA Ea HR 1.65 (1.51-1.80, Chi-squ 120, p<.0001); PAPi HR 0.84 (0.80-0.89, Chi-squ 48, p<.0001) and TAPSE/PASP HR 0.32 (017-0.60, Chi-squ 12, p=.0004). Conclusion(s) In patients with significant TR, PA Ea is highly feasible and higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify disease severity in patients with significant TR. Table Assoc. of PA Ea with mortality in TR

Abstract Aims The effects of obesity on Fontan haemodynamics are poorly understood. Accordingly, we assessed its impact on exercise invasive haemodynamics and exercise capacity. Methods and results Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) were retrospectively identified using an institutional database and categorized according to the presence of obesity [body mass index (BMI) > 30 kg/m2] and overweight/normal BMI (BMI ≤ 30 kg/m2). There were 18 individuals with obesity (BMI 36.4 ± 3 kg/m2) and 59 with overweight/normal BMI (BMI 24.1 ± 3.6 kg/m2). Peak oxygen consumption (VO2) on non-invasive cardiopulmonary exercise testing was lower in patients with obesity (15.6 ± 3.5 vs. 19.6 ± 5.8 mL/kg/min, P = 0.04). At rest, systemic flow (Qs) [7.0 (4.8; 8.3) vs. 4.8 (3.9; 5.8) L/min, P = 0.001], pulmonary artery (PA) pressure (16.3 ± 3.5 vs. 13.1 ± 3.5 mmHg, P = 0.002), and PA wedge pressure (PAWP) (11.7 ± 4.4 vs. 8.9 ± 3.1 mmHg, P = 0.01) were higher, while arterial O2 saturation was lower [89.5% (86.5; 92.3) vs. 93% (90; 95)] in obesity compared with overweight/normal BMI. Similarly, patients with obesity had higher exercise PA pressure (29.7 ± 6.5 vs. 24.7 ± 6.8 mmHg, P = 0.01) and PAWP (23.0 ± 6.5 vs. 19.8 ± 7.3 mmHg, P = 0.047), but lower arterial O2 saturation [82.4 ± 7.0% vs. 89% (85; 92), P = 0.003]. Conclusion Adults post-Fontan with obesity have worse aerobic capacity, increased Qs, higher filling pressures, and decreased arterial O2 saturation compared with those with overweight/normal BMI, both at rest and during exercise, mirroring the findings observed in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve haemodynamics and outcomes requires further study.

Abstract Aims To test whether an index based on the combination of demographics and body volumes obtained with a multisensor 3D body volume (3D-BV) scanner and biplane imaging using a mobile application (myBVI®) will reliably predict the severity and presence of metabolic syndrome (MS). Methods and results We enrolled 1280 consecutive subjects who completed study protocol measurements, including 3D-BV and myBVI®. Body volumes and demographics were screened using the least absolute shrinkage and selection operator to select features associated with an MS severity score and prevalence. We randomly selected 80% of the subjects to train the models, and performance was assessed in 20% of the remaining observations and externally validated on 133 volunteers who prospectively underwent myBVI® measurements. The mean ± SD age was 43.7 ± 12.2 years, 63.7% were women, body mass index (BMI) was 28.2 ± 6.2 kg/m2, and 30.2% had MS and an MS severity z-score of −0.2 ± 0.9. Features β coefficients equal to zero were removed from the model, and 14 were included in the final model and used to calculate the body volume index (BVI), demonstrating an area under the receiving operating curve (AUC) of 0.83 in the validation set. The myBVI® cohort had a mean age of 33 ± 10.3 years, 61% of whom were women, 10.5% MS, an average MS severity z-score of −0.8, and an AUC of 0.88. Conclusion The described BVI model was associated with an increased severity and prevalence of MS compared with BMI and waist-to-hip ratio. Validation of the BVI had excellent performance when using myBVI®. This model could serve as a powerful screening tool for identifying MS.