Citations

Abstract Aims The pathophysiology of tricuspid regurgitation (TR) during exercise in heart failure with preserved ejection fraction (HFpEF) is not well understood. Methods and results We investigated dynamic changes in TR severity during exercise in patients with HFpEF and associated relationships with haemodynamics, cardiopulmonary reserve, and prognosis using invasive haemodynamic exercise testing with simultaneous echocardiography and expired gas analysis. Among 169 patients with HFpEF (91 no TR, 44 mild TR, 34 ≥ moderate TR), older age and atrial fibrillation were more common in patients with greater TR severity. Right heart remodelling and dysfunction were more frequently observed with greater TR severity, particularly in the right atrium, along with stepwise increases in right atrial (RA) pressure and interventricular septal flattening, and decreases in cardiac output (CO). During exercise, TR severity frequently worsened, and over half of the patients with moderate TR at rest displayed severe TR during exercise, accompanied by profound RA dilatation, reduced RA reservoir strain, increased septal flattening, and more severely impaired CO reserve. Abnormalities in tricuspid annular motion and ventricular interaction were amplified by exercise with greater TR, but exercise pulmonary vascular pressures did not differ across groups. Patients with ≥ moderate TR during exercise displayed higher event rates (hazard ratio 2.85, 95% confidence interval 1.18–6.85), but patients with mild TR had similar prognosis as those without TR in adjusted models. Conclusions Tricuspid regurgitation in HFpEF is related to advanced RA myopathy and often worsens during exercise leading to dynamic right-sided heart failure, exaggerated ventricular interaction, impaired CO reserve, and increased risk for adverse outcomes. These data emphasize the clinical importance of exercise evaluation and call for further study of novel treatments in those with significant resting and provocable TR.

ABSTRACT Aims The impact of treatment for tricuspid regurgitation (TR) across different levels of left ventricular ejection fraction (LVEF) remains uncertain. This study aimed to compare the outcomes of surgical and transcatheter tricuspid valve interventions (TTVI) to conservative (medical) management across LVEF categories. Methods and results Patients with severe isolated TR from the TRIGISTRY, a multicentre international registry, were categorized based on LVEF (preserved ejection fraction [pEF]: ≥50%, mildly reduced ejection fraction [mrEF]: 41–49%, and reduced ejection fraction [rEF]: ≤40%). We assessed the impact of treatment modality and procedural success (mild-to-moderate or lower residual TR) on 2-year survival within each LVEF category. Among 2384 patients, 1383 had pEF, 400 had mrEF, and 601 had rEF. Compared to conservative management, surgery (p < 0.0005) and TTVI (p < 0.0001) were associated with a survival benefit in patients with pEF. No significant survival advantage was observed in patients with mrEF (p = 0.28 for both), nor in those with rEF (p = 0.76 and p = 0.22, respectively). Similar results were obtained when surgical and transcatheter interventions were grouped (p < 0.0001, p = 0.17 and p = 0.29 in patients with pEF, mrEF and rEF, respectively). Patients with residual TR after TTVI exhibited a trend toward worse survival compared to those managed conservatively across all LVEF categories (p = 0.47, p = 0.33 and p = 0.008 in pEF, mrEF and rEF, respectively). Conclusions Transcatheter tricuspid valve intervention, whether surgical or transcatheter-based, was associated with improved survival in patients with pEF but not in those with mrEF or rEF. Residual TR remained a significant prognostic factor across the entire LVEF spectrum. These findings highlight the need for careful patient selection when considering TTVI in individuals with rEF.

Importance Obesity is associated with a higher risk of recurrence, mortality, comorbidities, treatment-related adverse effects, and poor quality of life in patients with breast cancer. Scalable interventions are needed to promote weight loss in this population. Objective To evaluate the impact of a remotely delivered weight loss intervention (WLI) on weight change at 1 year in patients with breast cancer and obesity and to explore factors associated with weight change. Design, Setting, and Participants The Breast Cancer Weight Loss trial is a phase 3, randomized clinical trial evaluating the impact of a telephone-based WLI on invasive disease–free survival and other outcomes in women with obesity and early breast cancer at 637 sites across the US and Canada. Participants were enrolled to the study between August 2016 and February 2021. Participants included women with stage II to III, ERBB2 -negative breast cancer and a body mass index (BMI) of 27 or higher. Interventions Participants were randomized to a 2-year, telephone-based WLI plus health education or health education alone control group. Main Outcome and Measures The primary end point for this prespecified secondary analysis was weight change at 1 year. Weight was measured at baseline and 1 year, and changes in weight were compared between groups. Weight change was evaluated with a linear mixed-effects model including treatment group, weight over time, a time-by-group interaction, menopausal status, race and ethnicity, and hormone receptor status. Results A total of 3180 women with breast cancer and BMI of 27 and higher were included in the study; 1591 were randomized to the WLI and 1589 to the control group. At baseline, the mean (SD) age of participants was 53.4 (10.6), and the mean (SD) BMI was 34.4 (5.6). The racial and ethnic breakdown included 406 (12.8%) Black, 231 (7.3%) Hispanic or Latino, 2906 (91.4%) non-Hispanic, and 2555 (80.3%) White participants. WLI participants lost a mean of 4.3 kg (95% CI 3.9-4.6 kg), or 4.7% (95% CI, 4.3%-5.0%) of baseline body weight at 1 year vs control participants, who gained 0.9 kg (95% CI, 0.5-1.3 kg), or 1.0% (95% CI 0.1%-1.4%) of baseline body weight ( P < .001). Participants randomized to WLI experienced significant weight loss (vs control group participants) across demographic and tumor factors. WLI effect differed significantly by menopausal status, with postmenopausal participants having greater weight loss than premenopausal participants, and by race and ethnicity, with Black and Hispanic participants having less weight loss compared to other races and ethnicities. Conclusions and Relevance In this secondary analysis of a randomized clinical trial, a telephone-based WLI induced significant weight loss in patients with breast cancer with overweight and obesity across demographic and treatment factors. Further follow-up of the Breast Cancer Weight Loss trial will evaluate whether the WLI improves disease outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT02750826

Abstract Background and Aims The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy vs medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. Methods The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR, and randomized 2:1 to TTVR (n = 267) or control (n = 133). In a post hoc analysis, patients were stratified into severe TR (n = 172) and massive/torrential TR (n = 220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan–Meier estimates for all-cause mortality and heart failure (HF) hospitalization assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. Results One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe {1.64 [95% confidence interval (CI): 1.11, 2.43]} and massive/torrential [2.20 (1.55, 3.14)]. At 18 months, TTVR patients had similar mortality to controls [rate difference: severe 0.2% (−11.6, 11.9), massive/torrential −5.8% (−17.6, 6.0)], whereas HF hospitalization rates favoured TTVR in the massive/torrential cohort [vs control, severe 9.8% (−3.0, 22.7), massive/torrential -15.2% (−28.9, −1.5)]. Conclusions Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.

Objective: The objective of this study was to systematically review the literature-reported outcomes of CRYO compared to standard of care without CRYO (non-CRYO) after PEx repair. Summary Background Data: Surgical repair of pectus excavatum (PEx) via the Nuss or Ravitch procedures is associated with substantial postoperative pain. Intercostal nerve cryoablation (CRYO) performed during the primary surgical repair has been adopted as a non-opioid modality for pain management. Methods: A literature search was conducted in PubMed, Embase, and using additional online approaches to identify comparative studies of patients undergoing the Nuss or Ravitch procedure for PEx repair with CRYO versus non-CRYO between years 2014-24. Meta-analysis was performed to quantitatively evaluate primary outcomes of hospital length of stay (LOS) and opioid consumption. Secondary outcomes were hospital costs and complications, summarized qualitatively. Results: Of 178 studies, 32 comparative studies encompassing 13,103 patients were included; 28% (n=3,620) received CRYO. Random effects meta-analyses demonstrated a significantly shortened LOS by 1.8 days (95% confidence interval [CI]: -2.12, -1.42) and a significant reduction in inpatient and outpatient opioid consumption with CRYO by 186 morphine mg equivalents (MME) (95% CI: -262.26, -109.08) and 147 MME (95% CI: -255.72, -38.26), respectively. Complications with CRYO were either decreased or similar between groups and resolved over time. Hospital costs were similar. Conclusions: This systematic review suggests CRYO during PEx repair is associated with a significantly shorter hospital LOS, as well as decreased opioid consumption both in the hospital and after discharge. Complications were infrequent and time-limited.

ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.

PURPOSE Survivors of adolescent and young adult (AYA)-onset cancers require comprehensive cancer surveillance care. Guidelines recommend 1-4 clinician visits annually for 5 years depending on stage and disease. The goal of this study was to identify factors associated with patterns of post-treatment primary and oncology care in a large cohort of survivors of AYA-onset cancers diagnosed within an integrated health care system. METHODS Patients diagnosed with cancer between 2006 and 2020 age 15-39 years were included. Surveillance visits were identified from electronic medical records 2-5 years after diagnosis. Multivariable logistic regression was used to assess associations with zero oncology specialty visits. RESULTS Of 7,925 survivors, 46% were Hispanic, 6% non-Hispanic Black, 11% non-Hispanic Asian, 35% non-Hispanic White, and 65% female. One-quarter had no oncology specialty visits in the first surveillance year rising to 38% in year 5; 31% had 3+ visits in the first year, declining to 13% in year 5. Over the surveillance period, 17% did not have any oncology specialty visits and 6% had no primary care or oncology visits. Those who were male (odds ratio [OR], 1.21 [95% CI, 1.02 to 1.45]), 20-24 years at diagnosis (OR, 1.58, 95% CI, 1.27 to 1.9; v 35 to 39), or non-Hispanic Black (OR, 1.38, 95% CI, 1.05 to 1.82; v non-Hispanic White) or had high-deductible commercial or Medicaid insurance (OR, 1.35, 95% CI, 1.15 to 1.59; OR, 1.42, 95% CI, 1.11 to 1.82, respectively; v no or low deductible commercial) were more likely to be in the 0-visit group for oncology specialty care. CONCLUSION Although the majority of this cohort received either primary or oncology specialty care, our study identifies those who may need tailored outreach for follow-up care. Continued research into development and testing of interventions to improve uptake of appropriate health care for survivors of AYA-onset cancers is critical.

561 Background: Obesity and other lifestyle factors are associated with breast cancer (BC) risk and outcomes. These relationships appear to vary in pre- vs postmenopausal women. Here we explore associations between pathological features, diet quality and physical activity (PA) in patients (pts) with BC enrolled in the BWEL (Alliance for Clinical Trials in Oncology A011401) trial, stratifying for menopausal status. Methods: BWEL is a phase III trial evaluating the impact of a weight loss intervention on disease outcomes in 3180 pts with stage II-III HER2– BC and body mass index ≥27 kg/m 2 . The first 542 BWEL pts underwent assessment of PA (7-Day PA Recall) and diet (24-hour Diet Recall) at enrollment. Healthy Eating Index 2020 (HEI) score (0-100, higher value = healthier diet) and minutes/week (min/wk) of moderate/vigorous PA (MVPA) were calculated. Estrogen receptor (ER) and progesterone receptor (PR) expression level (%) were abstracted from pathology reports. Analyses of links between HEI score, MVPA min/wk, % ER/PR, stratified by menopausal status, were conducted using t-tests; differential associations by menopausal status used linear regression models with interaction term. Results: In 523 pts with available pathology data, 76.5% had ER/PR+ BC, 56.2% were postmenopausal. Median HEI score was 50.1 (range 18.1-96.4), median MVPA min/wk was 0 (range 0-630), median time from diagnosis to enrollment was 10.0 months (range 2.4-13.1). In postmenopausal pts, higher diet quality was linked to increased % ER and PR (HEI above vs below median, mean % ER 78.0 vs 66.1, p=0.012; mean % PR 57.7 vs 43.1, p=0.004). The relationship between HEI score and % ER/PR differed significantly by menopausal status (interaction term of menopausal status and % ER: p=0.006; and % PR: p=0.012); there were no significant associations between HEI scores and % ER/PR in premenopausal pts. There were no significant associations between PA and % ER/PR. Conclusions: Healthier diet was associated with higher % ER and PR in postmenopausal pts with BC, but no relationship was seen in premenopausal pts. These data suggest that lifestyle factors may influence BC pathologic features related to outcomes in older women. Support: U10CA180821, U10CA180882, UG1CA189823, U24CA196171, https://acknowledgments.alliancefound.org . Clinical trial information: NCT02750826 . % ER mean (SD) p value % PR mean (SD) p value Post-Menopausal HEI* score≤50.1 [n=134]>50.1 [n=156] 66.1 (43.3)78.0 (36.8) 0.012 43.1 (41.8)57.7 (41.0) 0.004 MVPA † min/wk0 [n=147]≥1 [n=147] 74.5 (39.3)70.3 (41.2) 0.37 50.0 (41.8)53.0 (42.0) 0.41 Pre-Menopausal HEI* score≤50.1 [n=124]>50.1 [n=103] 70.5 (38.5)65.5 (43.0) 0.15 53.5 (41.1)49.1 (43.0) 0.43 MVPA † min/wk0 [n=112]≥1 [n=113] 66.3 (41.0)66.3 (41.2) 0.99 49.5 (41.4)52.6 (42.7) 0.59 *Healthy Eating Index. † Moderate/Vigorous Physical Activity.