Summary Scores Research Articles

Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial

Background: In the phase 3 randomized controlled study, ATTRibute-CM, acoramidis, a transthyretin (TTR) stabilizer, demonstrated significant efficacy on the primary endpoint. Participants with transthyretin amyloid cardiomyopathy (ATTR-CM) who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE. Methods: Participants who previously received acoramidis through Month 30 (M30) in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through M30 were switched to acoramidis (placebo to acoramidis). Participants who received concomitant tafamidis in ATTRibute-CM were required to discontinue it to be eligible to enroll in the OLE. Clinical efficacy outcomes analyzed through Month 42 (M42) included time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH), ACM alone, first CVH alone, ACM or recurrent CVH, change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), serum TTR, and the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS). Safety outcomes were analyzed through M42. Results: Overall, 438 of 632 participants in ATTRibute-CM completed treatment and 389 enrolled in the ongoing OLE (263 continuous acoramidis, 126 placebo to acoramidis). The hazard ratio (HR) (95% CI) for ACM or first CVH was 0.57 (0.46, 0.72) at M42 based on a stratified Cox proportional hazards model ( P -value < 0.0001) favoring continuous acoramidis. Similar analyses were performed on ACM alone and first CVH alone, with HRs (95% CI) of 0.64 (0.47, 0.88) and 0.53 (0.41, 0.69), respectively, at M42. Treatment effects for NT-proBNP and 6MWD also favored continuous acoramidis. Upon initiation of open-label acoramidis in the placebo-to-acoramidis arm there was a prompt increase in serum TTR. Quality of life assessed by KCCQ-OS was well preserved in continuous acoramidis participants compared with the placebo to acoramidis participants. No new clinically important safety issues were identified in this long-term evaluation. Conclusions: Early initiation and continuous use of acoramidis in the ATTRibute-CM study through M42 of the ongoing OLE study was associated with sustained clinical benefits in a contemporary ATTR-CM cohort, with no clinically important safety issues newly identified.

Associations of physical activity and sedentary time with health-related quality of life in patients with localized renal cell cancer: a cross-sectional analysis within the ReLife study

Abstract Purpose This study examined the associations of device-measured moderate-to-vigorous physical activity (MVPA) and sedentary time as well as self-reported MVPA with health-related quality of life (HRQoL) in patients with localized renal cell cancer (RCC) in the recovery phase after surgery. Methods At 3 months post-surgery, 341 patients with stage I-III RCC participating in the ReLife study wore an ActivPAL3 device to determine MVPA and sedentary time. The SQUASH questionnaire was used for assessing self-reported MVPA, and the EORTC QLQ-C30 for assessing HRQoL (range 0–100). Multivariable linear regression models were used to examine the cross-sectional associations of MVPA and sedentary time with HRQoL. Results The highest (≥ 6.7 h/week) versus lowest (≤ 2.7 h/week) quartile of MVPA was associated with a better global health status (β, 10.2; 95% CI, 5.1, 15.3), summary score (β, 4.6; 95% CI, 1.1, 8.1), physical (β, 7.7; 95% CI, 3.8, 11.6), role (β, 12.4; 95% CI, 4.7, 20.2), and social functioning (β, 7.3; 95% CI, 0.2, 14.4), and lower fatigue (β, − 11.2; 95% CI, − 18.1, − 4.2). Results for self-reported MVPA were in the same direction but weaker. The lowest (≤ 8.8 h/day) versus highest (≥ 11.5 h/day) quartile of sedentary time was associated with better physical functioning (β, 4.6; 95% CI, 0.8, 8.5). Conclusions In patients with localized RCC, higher MVPA 3 months post-surgery was associated with better HRQoL outcomes including less fatigue whereas lower sedentary time was only associated with better physical functioning. This information can contribute to the development of physical activity guidelines and interventions to improve HRQoL.

A combination of clinical, electrocardiographic, and echocardiographic parameters predicts pulmonary hypertension occurrence in patients with end-stage renal disease

BackgroundPulmonary hypertension (PH) in patients with end-stage renal disease (ESRD) has a high incidence rate and mortality and its early identification is critical. However, whether a combination of clinical, electrocardiographic, and echocardiographic parameters can predict the occurrence of PH in patients with ESRD remains to be elucidated. Herein, we evaluated the predictive value of the combined score of these parameters.MethodsData from 370 patients with newly diagnosed ESRD who underwent routine echocardiography and electrocardiography between May 2016 and May 2017 were retrospectively evaluated. The incidence of PH during a 60-month follow-up period was investigated. Twenty-one patients were excluded due to incomplete data among other reasons. Finally, 349 patients were included in the analysis, of whom, 158 (45%) developed PH.ResultsAnalysis of electrocardiogram reports suggested that a corrected Q-T interval (QTc) of >438.5 ms was associated with PH. Echocardiographic reports suggest that left atrial diameter (LAD), interventricular septum thickness in end-diastole (IVSd), stroke volume (SV), and pericardial effusion are also associated with PH development. Results of multivariate Cox analysis showed that LAD >3.785 cm, IVSd >1.165 cm, SV >79.5 ml, QTc >438.5 ms, and pericardial effusion were independent predictors of PH in patients with ESRD. The incidence of new-onset PH increased significantly with increasing composite scores, that is, the sum of risk scores determined using hazard ratios.ConclusionsA total score that includes a combination of parameters such as LAD >3.785 cm, IVSd>1.165 cm, SV >79.5 ml, QTc >438.5 ms, and pericardial effusion can help describe the risk of new-onset PH.

Menstrual cycle related depressive symptoms and their diurnal fluctuations – an ambulatory assessment study

Abstract Background Reproductive mood disorders indicate that within-person variation in depressive symptoms across the menstrual cycle can be related to ovarian hormone changes. Until now, such cycle-related symptom changes have been measured once daily, even though depression research indicates systematic diurnal changes in symptoms. Further, previous research often focused on aggregated depression scores. This study examined whether three daily assessments of depressive symptoms follow similar trajectories across the menstrual cycle and investigated within-person cyclical fluctuation of all individual symptoms and the aggregated score. Methods 77 naturally-cycling participants (35 with and 42 without depressive disorder) provided three daily ratings of depressive symptoms across one menstrual cycle to evaluate individual and summarized symptoms. Results Reliability estimates (w) of the three diurnal measurements ranged from 0.56 to 0.78. Cyclicity showed statistically significant interindividual differences for all symptoms, and individual symptoms differed significantly from each other in their magnitude of cyclicity. Limitations Only one menstrual cycle was assessed to reduce participant burden. Further, ovulation testing dates were based on self-reported cycle lengths, and only LH (luteinizing hormone) peaks were tested without subsequent progesterone rises. Conclusions The results highlight the need for a symptom-specific approach to assess individual variance in cyclicity of depressive symptoms. Reliability for one daily assessment can be improved by using the afternoon value, a sum score for depressiveness, or multiple items per symptom. Furthermore, this study emphasizes, that depressive symptoms can systematically change across the menstrual cycle, and it is, therefore, important to include it in depression research. Exploring female-specific risk factors of depression will enable the development of person-tailored treatments. Trial registration The study was preregistered at ClinicalTrials.gov (NCT04086316) with the first registration on 27/08/2019.

Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial

AbstractPatients with obesity-related heart failure with preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular–kidney end-organ damage. In the SUMMIT trial, patients with HFpEF and obesity were randomized to the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide (n = 364, 200 women) or placebo (n = 367, 193 women). As reported separately, tirzepatide decreased cardiovascular death or worsening heart failure. Here, in this mechanistic secondary analysis of the SUMMIT trial, tirzepatide treatment at 52 weeks, as compared with placebo, reduced systolic blood pressure (estimated treatment difference (ETD) −5 mmHg, 95% confidence interval (CI) −7 to −3; P < 0.001), decreased estimated blood volume (ETD −0.58 l, 95% CI −0.63 to −0.52; P < 0.001) and reduced C-reactive protein levels (ETD −37.2%, 95% CI −45.7 to −27.3; P < 0.001). These changes were coupled with an increase in estimated glomerular filtration rate (ETD 2.90 ml min−1 1.73 m−2 yr−1, 95% CI 0.94 to 4.86; P = 0.004), a decrease in urine albumin–creatinine ratio (ETD 24 weeks, −25.0%, 95% CI −36 to −13%; P < 0.001; 52 weeks, −15%, 95% CI −28 to 0.1; P = 0.051), a reduction in N-terminal prohormone B-type natriuretic peptide levels (ETD 52 weeks −10.5%, 95% CI −20.7 to 1.0%; P = 0.07) and a reduction in troponin T levels (ETD 52 weeks −10.4%, 95% CI −16.7 to −3.6; P = 0.003). In post hoc exploratory analyses, decreased estimated blood volume with tirzepatide treatment was significantly correlated with decreased blood pressure, reduced microalbuminuria, improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and increased 6-min walk distance. Moreover, decreased C-reactive protein levels were correlated with reduced troponin T levels and improved 6-min walk distance. In conclusion, tirzepatide reduced circulatory volume–pressure overload and systemic inflammation and mitigated cardiovascular–kidney end-organ injury in patients with HFpEF and obesity, providing new insights into the mechanisms of benefit from tirzepatide. ClinicalTrials.gov registration: NCT04847557.

Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire: A Patient-Level Meta-Analysis.

The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a commonly used outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean treatment effects do not necessarily reflect the clinical benefit experienced by individual patients. To evaluate the association between mean KCCQ treatment effects and the proportions of patients experiencing clinically important improvements across a range of clinical trials and heart failure etiologies. A patient-level analysis of 11 randomized clinical trials, including 9977 patients, was performed to examine the association between mean treatment effects and the KCCQ Overall Summary Score (OSS) and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate to large (≥10 points) improvements. There was no target date range, and included studies were those for which patient-level data were available. Validation was performed in 7 additional trials. The data were analyzed between July 1 and September 15, 2023. Proportion of patients experiencing an improvement of 5 or more and 10 or more points in their KCCQ score (with each domain transformed to a range of 0 to 100 points, where higher scores represent better health status). Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI], 4.0%-8.1%) in the proportion of patients improving 5 or more points and 5.0% (95% PI, 3.1%-7.0%) in the proportion improving 10 or more points, corresponding to a number needed to treat of 17 (95% PI, 12-25) and 20 (95% PI, 14-33), respectively. Inferences about clinical impacts based on population-level mean treatment effects may be misleading, since even small between-group differences may reflect clinically important treatment benefits for individual patients. Results of this study suggest that clinical trials should explicitly describe the distributions of KCCQ change at the patient level within treatment groups to support the clinical interpretation of their results.

Effect of acupuncture on quality of life in atrial fibrillation: study protocol for a randomised controlled trial

IntroductionAtrial fibrillation (AF) is the prevalent cardiac arrhythmia and can significantly impair the quality of life (QoL). Although catheter ablation (CA) is an established treatment for AF,post-procedural complications or perceived...

Within-person, longitudinal associations between neighborhood cohesion and adult mental health: A test of bidirectional relations.

There is theory and evidence supporting a relationship between neighborhood cohesion and mental health among adult people. However, most studies have used a cross-sectional design, and longitudinal studies have provided mixed support for this hypothesis. Moreover, while neighborhood cohesion is assumed to be a consistent predictor of mental health, the possibility of a reciprocal relation has been overlooked. The aim of the current study was to investigate the within-person reciprocal associations between neighborhood cohesion and adult mental health. This study used data from Understanding Society: the UK Household Longitudinal Study including waves 1, 3, 6, 9, and 12 (n = 81,895). A short version of Buckner's Neighborhood Cohesion Instrument was used, along with two well-established measures of mental health: the 12-item General Health Questionnaire and the mental component summary score of the 12-item Short-Form Health Survey. Hierarchical Bayesian continuous time dynamic modeling revealed significant reciprocal within-person cross-effects (i.e. deterministic effects) between neighborhood cohesion and adult mental health, a larger standardized effect of mental health on neighborhood cohesion than than vice versa. Moreover, peak standardized cross-lagged effects were found for a time interval of approximately 1 year. Finally, the combined stochastic and deterministic interpretation revealed effects of neighborhood cohesion on mental health that were opposite to what was expected, suggesting a faster dissipation of some initially correlated change. Although neighborhood cohesion has traditionally been conceptualized in terms of its contribution to mental health, there is greater support for the view that mental health precedes neighborhood cohesion rather than the reverse.

Impact of Enhanced Recovery After Surgery (ERAS) Protocols on Outcomes Up to Two Years After Adult Structural Spine Disorder Surgery

Study Design. Retrospective cohort study of prospectively enrolled database Objective. We analyze the recovery pattern of Adult Structural Spine Disorder (ASD) patients who underwent corrective surgery with Enhanced Recovery After Surgery protocol (ERAS+), including physical and psychological prehabilitation components, compared to non-ERAS protocol (ERAS-) up to 2-years after surgery. Summary of Background Data. Spine surgery for ASD is often highly invasive, which can contribute to prolonged recovery. The trajectory of recovery may be accelerated by the application of enhanced recovery principles. Methods. Inclusion criteria were operative patients with ASD>18yrs with complete baseline, 90 days perioperative, and 2-year postoperative data. We assessed differences in baseline demographics, surgical details, baseline Health-Related Quality of Life (HRQL), and surgical outcomes between ERAS+ and ERAS- patients. Outcomes included adverse events, reoperations, and radiographic parameters such as sacral slope (SS), pelvic tilt (PT), pelvic incidence-lumbar lordosis (PI-LL) mismatch, sagittal vertical axis (SVA), lumbar lordosis (LL), T2–T12 kyphosis, and maximum Cobb angle. Additionally, HRQL measures included the PCS, ODI, NDI, EQ-5D, SRS-22r total and domain scores, NRS-Back, and NRS-Leg. We used multivariable logistic regression and ANCOVA to adjust for confounding. Results. 471 patients with ASD met inclusion criteria, with 59 designated ERAS+. Those individuals ERAS+ were older (64.1±13.0 vs. 58.0±16.0;P=0.005), had a higher CCI, (2.4±1.8 vs. 1.4±1.6;P<0.001), and exhibited a higher modified ASD frailty index (8.2±5.4 vs. 6.3±4.9;P=0.019). Adjusted analysis demonstrated the ERAS+ cohort demonstrated lower likelihood of overall reoperations (OR:0.3; 95%CI:0.13-0.89), and a lower likelihood of overall adverse events (OR:0.4;CI95%:0.19-0.93). ERAS+ was more likely to achieve the MCID in the SRS-22r Total scores at 6 months(OR:3.1;CI95%:1.2-8.4), self-image domain at 6 months (OR:9.0;CI95%:1.6-50.0), in the pain domain at 6 months (OR:3.5;CI95%:1.01-11.9) and 1 year postoperatively (OR:2.6;CI95%:1.03-6.7), and in the SF-36’s physical component summary scores (PCS) at 1 year (OR:2.1;CI95%:1.05-4.2). No other statistically significant differences in HRQL were observed at the remaining time points (P>0.05). Conclusion. Our work is the first to evaluate HRQL metrics and complication over two-years following ASD correction with ERAS. Despite presenting with more severe baseline frailty and higher comorbidity profiles, patients with ASD who underwent corrective surgery with an ERAS protocol experienced fewer short-term adverse events, and improved HRQL. We believe ERAS following ASD surgery leads to faster functional recovery, reduced postoperative deconditioning, and improved quality of life.

Abstract 4128187: Does Health-related Quality of Life Differ by Race over time in Older Patients with Heart Failure from Before to After Heart Transplantation or Long-term Mechanical Circulatory Support?

Background: Minority patients are disproportionately affected by heart failure. Therefore, we aimed to determine the impact of race on health-related quality of life in three groups of older patients (60-80 years) with heart failure who underwent advanced surgical therapies (within race and by surgery group): (1) heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS]), (2) HT without pre-transplant MCS (HT Non-MCS), or (3) long-term MCS, if ineligible for HT. Methods: Secondary analyses were conducted using data from the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support study. From 10/1/15 to 12/31/18, 396 patients with heart failure were recruited at 13 U.S. medical centers, of which 305 patients underwent HT (n=161 [68 HT MCS and 93 HT Non-MCS]) or long-term MCS (n=144) and had data through 1 year follow-up. Analysis included non-inferiority testing (Long-term MCS vs HT MCS; Long-term MCS vs HT Non-MCS). To demonstrate non-inferiority, the surgical strategies by race needed to show a difference of at least 5 percentage points, with a 95% lower confidence boundary and a two-tailed p-value<0.05 in health-related quality of life, using the Kansas City Cardiomyopathy-12 Questionnaire Overall Summary Score at baseline and 3-, 6-, and 12 months. Results: The entire cohort was on average 66.2±4.7 years, 78% male, and 84% White. All three surgical groups experienced improved health-related quality of life from before to 1 year follow-up; with the largest gain through 3-months. Using non-inferiority testing, the long-term MCS minority group did not demonstrate non-inferiority when compared to both the HT MCS minority group and HT Non-MCS minority group confidence limits above the non-inferiority margin of -5 (Figure). Also, the White long-term MCS group did not demonstrate non-inferiority when compared to the White HT MCS and White HT Non-MCS groups. Conclusion: Differences in health-related quality of life among groups based on race were not statistically significant. Per non-inferiority testing, HT is superior to long-term MCS for health-related quality of life, regardless of race.

Abstract 4136785: Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire

Introduction: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a common outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean effects do not necessarily reflect the clinical benefit experienced by patients. Objectives: To evaluate the relationship between mean KCCQ treatment effects in clinical trials and the proportions of patients experiencing clinically important improvements across a range of heart failure etiologies and interventions. Methods: We performed a patient-level meta-analysis of 11 randomized trials (9,977 patients) to examine the relationship between mean KCCQ Overall Summary Score (OSS) treatment effects and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate or larger (≥10 points) improvements. Validation was performed in 7 additional trials. Results: Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI] 4.0-8.1) in the proportion of patients improving ≥5 points and 5.0% (95% PI 3.1-7.0) in the proportion improving ≥10 points, corresponding to NNTs of 17 (95% PI 12-25) and 20 (95% PI 14-33), respectively. Similar relationships were observed in the validation studies. Conclusions: Inferences on clinical impact based on population-level mean treatment effects are misleading since even small between group differences may reflect clinically important treatment benefits at the patient level. Clinical trials should explicitly describe the distributions of patient-level KCCQ changes to support clinical interpretation of their results.

Socioeconomic status and adherence to COVID-19 preventative measures in Australia: A national cohort study.

The uptake of recommended preventative measures is a critical concern for protecting the public against COVID-19 outbreaks and future pandemics. However, it is unclear to what extent COVID-19 preventative measures were followed in Australia. This study aims to determine adherence level to COVID-19 preventative measures in 2021, and whether these were associated with socioeconomic status (SES). This was a national cross-sectional study using data from the Household Income and Labour Dynamics in Australia (HILDA) survey. This study included 15 457 community-dwelling adults (18 years or older) who participated in the 2021 wave of HILDA survey. SES was assessed by the Socio-Economic Index For Areas (SEIFA) score, split into quintiles. Outcomes included self-reported adherence to COVID-19 preventative measures (mask wearing, keeping distance, staying home; sum score range 3-15) and COVID-19 status (yes/no). Linear and logistic regression were used accordingly to assess the association between SES and the sum score of adherence to COVID-19 measures, and COVID-19 vaccination status. Adherence to COVID-19 preventative measures and uptake of COVID-19 vaccine in Australia in 2021 were moderate (between 60% and 70%). Regression models showed higher SES was associated with a slightly higher score of adherence (β = .08, 95% CI = .04-.12) and a higher likelihood of self-reporting receiving COVID-19 vaccination (OR 1.27, 95% CI = 1.23-1.31). SES was positively associated with the level of adherence to COVID-19 preventative measures and the probability of receiving COVID-19 vaccine. The findings of this study highlight the potential benefits of considering SES, particularly its impact on equity and access, when designing an educational program or awareness campaign in times of crisis. SO WHAT?: The findings of this study highlight the importance of considering SES when designing an educational program or an awareness campaign in times of crisis.

Abstract 4143258: Sex Differences in Health Status Outcomes: Analysis of the ISCHEMIA Randomized Clinical Trial

Background: Despite a lesser extent and severity of coronary artery disease (CAD), women had a higher burden of angina than men in the ISCHEMIA trial, suggesting that other factors may explain symptom severity in women. We aim to describe demographic and clinical characteristics, as well as differences in care patterns, associated with health status differences in women, as compared with men, in the conservative and invasive treatment groups of the ISCHEMIA trial. Methods: The ISCHEMIA trial randomized participants with moderate or severe ischemia to a routine invasive strategy of cardiac catheterization with complete revascularization plus guideline-directed medical therapy (GDMT), or an initial conservative strategy of GDMT alone with catheterization reserved for GDMT failure. Health status was a key secondary outcome. Using linear regression models we compared raw and adjusted Seattle Angina Questionnaire (SAQ) scores in women and men at baseline and at 1 year, stratified by randomized treatment strategy. Within the invasive strategy, sex differences were adjusted for completeness of revascularization among those with ≥1 coronary stenosis ≥70%. Results: Of 4,617 ISCHEMIA participants with valid SAQ data, women had lower (worse) baseline SAQ summary scores (SS) throughout follow up (Figure) after adjustment for demographics and clinical characteristics, including severity of CAD (difference 5.4 points, 95% CI 4.0-6.7). Women had lower SAQ SS after adjustment for post-randomization treatment (i.e., medical therapy, achievement of risk factor goals and, in the invasive strategy, complete revascularization), 2.4 points lower (95% CI 0.7-4.1) in the conservative group (Figure), and 1.9 points lower than in men (95% CI 0.1-3.7) in the invasive group. Findings were similar for all SAQ subscales. Conclusions: Women with chronic coronary disease in ISCHEMIA had worse health status than men at baseline and 1 year later, which was not explained by demographic or clinical characteristics, intensity of medical therapy, or completeness of revascularization.

Abstract 4126731: Cumulative Cardiovascular Health in Young Adulthood and Systemic Target Organ Damage: The Coronary Artery Risk Development In Young Adults (CARDIA) Study

Introduction: Cardiovascular health (CVH) in young adulthood (YA) is strongly associated with subclinical and clinical outcomes in later life. Longitudinal patterns of CVH exposure through YA (e.g., cumulative CVH exposure) may be particularly important. However, no studies have assessed cumulative CVH in YA and its association with target organ damage (TOD). Methods: CVH was defined using Life’s Essential 8 (LE8) score. CARDIA participants (ppts) with CVH assessed at ≥3 exams over 20 years of follow-up in YA (year [Y]0 to Y20 exams; mean ages 25 to 45 years) were included. Cumulative LE8 scores (cumLE8; higher = better CVH over time) were calculated as the sum of LE8 scores through YA carried forward between exams measured as point*years. Eight markers of TOD (listed in Results) were measured at subsequent exams (Y20 or Y25) including cardiac, renal, pulmonary, and neurologic markers. Associations of cumLE8 with markers of TOD were assessed using partial effects regression models adjusted for race, sex, and maximal education. Results: There were 3,485 ppts (43.4% men, 46.2% Black) with mean cumLE8 score of 1,448.6 (SD 211.4) point*years. Higher cumLE8 in YA was linearly associated with lower measures of cardiac (left ventricular mass index, carotid intima media thickness, prevalence of coronary artery calcium), renal (estimated glomerular filtration rate [eGFR] in men), and neurologic damage (proportion of white matter hyperintensity on brain MRI) ( Figure ). Higher cumLE8 was also linearly associated with better lung function (forced expiratory volume in 1 second, forced vital capacity). Urine albumin-creatinine ratio (in men and women) and eGFR (in women) were non-linearly associated with cumLE8. Conclusions: Our findings underscore the importance of high cumLE8 in YA and its association with reduced onset of TOD later in life. Primordial prevention strategies are needed to achieve and maintain high CVH through the critical period of YA.

Abstract 4127664: Influences of Age on Improvement of Health-Related Quality of Life in Patients with Atrial Fibrillation following Initial Treatment

Background: The prevalence of Atrial Fibrillation (AF), the most cardiac common arrhythmia, increases with age. Various treatment strategies are available to improve health-related quality of life (HRQoL) in patients with AF; however, the impact of age on HRQoL treatment benefits is unknown. Aims: To investigate the association of age with HRQoL benefit across different treatment strategies. Methods: Using data from a multicenter registry for outpatients with early recognized AF, HRQoL at enrollment and 1 year later was measured with the Atrial Fibrillation Effect on Quality-of-life quesTionnaire (AFEQT). The association between age and the 1-year changes in AFEQT-overall summary (OS) and subdomain scores with either rate or rhythm control strategies were assessed using generalized additive models (GAM) to address non-linear relationships. To support clinical interpretation, multivariable linear regression models were performed with categories of age ranges. Results: Among 2786 patients (31.7% women, 54.7% rhythm control); 946 were <65 of age, 1019 were ≥65–75, and 821 were ≥75 years old. Rhythm (vs. rate) control was pursued in 76.6%, 58.0%, and 33.6% and mean AFEQT-OS changes were 11.1 (SD 16.6), 8.0 (17.0), and 4.7 (18.2) in those aged <65, 65–74, and ≥75, respectively. The GAM showed improvements in AFEQT-OS attenuated with advancing age with both treatment strategies ( Figure ). Linear regression analyses showed lesser improvements in AFEQT-OS as higher age categories (≥65–75 vs. <65, β -1.12 [95% CI, -2.33 – 0.09]; ≥75 vs. <65, β -3.86 [-5.29 – -2.42]), which were mainly driven by lesser improvement in AFEQT-daily activities scores, without differences in AFEQT scores for symptom or treatment concerns ( Table ). Conclusions: In AF patients, HRQoL benefits after treatment were attenuated by advancing age, primarily driven by less improvement in functional limitations, underscoring the need for further research to identify optimal treatment strategies for older adults.

Evolocumab treatment reduces carotid intima-media thickness in paediatric patients with heterozygous familial hypercholesterolaemia.

Children with heterozygous familial hypercholesterolaemia (HeFH) show greater carotid intima-media thickness (cIMT). Evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody, substantially reduced low-density lipoprotein cholesterol (LDL-C) and modestly reduced lipoprotein(a) in children with HeFH. We investigated evolocumab's effect on cIMT progression. HAUSER-RCT was a randomised, placebo-controlled trial. 157 paediatric patients with FH (age: 10-17 years) and LDL-C >130mg/dL despite statin therapy received monthly evolocumab 420mg or placebo for 24 weeks. Patients who continued into an open-label extension (HAUSER-OLE; n=150) received 80 weeks of monthly evolocumab plus statins. cIMT was measured by B-mode ultrasound scanning of right and left common carotid artery at baseline; week 24 of RCT [day 1 OLE]; and weeks 24, 48, and 80 of OLE. Descriptive analysis of cIMT was a prespecified HAUSER secondary endpoint, and inferential tests reported here were post-hoc. 151 patients had evaluable cIMT summary scores at ≥1 visit. From RCT baseline to week 24, mean cIMT increased by 0.006mm (SD=0.05) with placebo (n=37) and decreased by 0.003mm (SD=0.05) with evolocumab (n=76). From RCT baseline to OLE week 80, mean cIMT summary score decreased by 0.019mm (SD=0.04) and 0.012mm (SD=0.05), respectively, in patients who initially received placebo (n=34, P=0.007) versus receiving evolocumab throughout (n=59, P=0.067). Across patients who received evolocumab in OLE, mean cIMT significantly decreased by 0.011mm (SD=0.05) from OLE day 1 to week 80 (n=94, P=0.034). In children with HeFH, evolocumab plus statin treatment up to 104 weeks led to regression in carotid arterial wall thickening.

Abstract 4122763: Health Status Outcomes of Antianginal Therapies in Patients After Coronary Revascularization: Insights From the GREAT Disease Registry Study

Background: The impact of antianginal therapies on the health status of coronary artery disease (CAD) patients who have undergone coronary revascularization has not been extensively researched. This study aimed to investigate the effect of nicorandil on the health status in patients after coronary revascularization, measured by the Seattle Angina Questionnaire (SAQ). Methods: We analyzed data from 1,556 patients enrolled in the GREAT Disease Registry Study (Clinicaltrial No. NCT05050773) between September 2021 and May 2022. Changes in SAQ summary score (SAQ-SS) from baseline to 3, 6, 9, and 12 months were assessed. Statistical methods included a linear mixed-effects model and propensity score matching (PSM) for comparative analysis. Results: Among the 1,038 patients receiving revascularization analyzed (22.7% female; mean age [SD], 59.9 [10.2] years), 648 (62.4%) received nicorandil, while 390 (37.6%) did not. In the linear mixed-effects model analysis, statistically significant improvements were observed with nicorandil in SAQ-SS across all time points ( Table 1 ), indicating beneficial effects of nicorandil on health status outcomes after revascularization. Sensitive analysis was conducted using the PSM method. After PSM adjustment, both groups comprised 321 patients each. The change in SAQ-SS from baseline to 12 months was significantly greater in the nicorandil group (19.2 ± 14.06 points) compared to the non-nicorandil group (14.91 ± 12.9 points, p < 0.001). Conclusions: These findings indicated that nicorandil is associated with improved health status outcomes in CAD patients who have undergone coronary revascularization.

Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p<0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.

Abstract 4129729: Relationship Between Inflammatory Biomarkers and Quality of Life in Black Adults Living with Heart Failure: A Pilot Study

Introduction: Heart failure (HF) impacts quality of life considerably, with inflammatory biomarkers potentially playing a significant role in this relationship. The purpose of this study is to examine the relationship between NYHA Class, inflammatory biomarkers, and quality of life in Black adults living with HF. Methods: Black adults living with HF (N=41) were enrolled in this study. NYHA Class was extracted from the medical record. Health-related quality of life was measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 23-item questionnaire that quantifies physical function, symptoms, social function, and health-related quality of life in HF. Scores are transformed to a range of 0-100, with higher scores reflecting better health status. One-way ANOVA and correlation analyses were used to assess associations between NYHA class, inflammatory biomarkers (XO activity, IL-1β, IL-15, and CCL-19), and KCCQ scores. Results: Participants were 57±11 years of age and 66% female, with mean LVEF 33±14%. NYHA Class ranged from I (20%) to IV (12%), with the majority of participants in Class II (34%) and III (22%). Mean KCCQ Clinical Summary Score was 85± 21. NYHA Class I had significantly lower scores on the KCCQ Clinical Summary Score compared to Class III and IV (p < .001, η 2 = 0.54), KCCQ Physical Limitation compared to Class II, III, and IV (p < .001, η 2 = 0.53), and KCCQ Symptom Frequency compared to Class IV (p = .001, η 2 = 0.39). The KCCQ Clinical Summary Score was negatively associated with XO activity (r = -0.440, p = .046), IL-1β (r = -0.407, p = .043), IL-15 (r = -0.427, p = .033), and CCL-19 (r = -0.559, p = .004). Similar negative associations were observed for the KCCQ subscales. Conclusion: The negative association between XO activity and health-related quality of life (KCCQ) in individuals with HF highlights the potential impact of oxidative stress on these patients' subjective well-being and functional status. Understanding this relationship could underscore the importance of mitigating oxidative stress pathways to improve the overall quality of life and symptom burden experienced by individuals with HF. The KCCQ and subscales were also negatively associated with markers of inflammation, highlighting the potential impact of systemic inflammatory processes on subjective well-being and functional status in persons with HF. Targeting inflammatory pathways may improve quality of life and mitigate the burden of symptoms in HF.

Abstract 4122256: Health Status Outcomes of Nicorandil in Patients With Angina Pectoris: A Prospective, Multicenter, Registry-Based Study

Background: Coronary artery disease (CAD) exerts a considerable impact on mortality from cardiovascular disease. Approximately half of patients with CAD initially present with angina pectoris. The GREAT study is designed to establish a large cohort of Chinese patients with angina pectoris and compare the effectiveness of different anti-angina regimens, using the Seattle Angina Questionnaire. Method: The GREAT (reGistRy study of medical thErapy in patients with Angina pecToris) Registry is a multicenter, prospective, observational, cohort study that enrolled 1556 adult CAD patients with angina pectoris from nine hospitals in China. The study included patients currently receiving or eligible to receive oral anti-anginal regimens. The cohort was classified into nicorandil and non-nicorandil groups based on the treatment therapies. The primary outcome was the Seattle Angina Questionnaire summary score (SAQ-SS) changes from baseline to 12 months. The SAQ-SS averages the domains of physical limitation, angina frequency, and quality-of-life scores. Results: From September 2021 to May 2022, a total of 1575 patients were screened, of whom 1556 met the inclusion criteria and were included ( Figure 1 ). Among the patients at the full analysis set (FAS, N=1528), 28.5% were women, and the median age was 61 years. Baseline variables were well balanced after propensity score matching, with both groups containing 450 patients. In the nicorandil group, patients showed a significantly greater increase in mean SAQ-SS score at Month 12 compared to the non-nicorandil group (17.6±14.0 vs 15.1±13.0; difference: 0.19; 95% CI, 0.05-0.32; p=0.003). In addition, patients in the nicorandil versus the non-nicorandil group reported a significantly greater mean improvement in the SAQ-QoL domain (18.9±21.4 vs 16.3±20.4; p=0.042) and SAQ-PL domain (11.7±16.9 vs 10.0±17.0; p=0.001). Over 12 months, a higher proportion of patients in the nicorandil group, compared to the non-nicorandil group, reported substantial improvements in SAQ-SS, with 24.1% experiencing large improvements (20-29 points) and 18.2% reporting very large improvements (≥30 points) versus 20.7% and 12.0%, respectively (p=0.005 across all categories) ( Figure 2 ). Conclusion: This real-world data indicates that nicorandil-based anti-angina regimens are associated with a greater health status outcome improvement compared to those not using nicorandil in CAD patients.