Clinical Summary Research Articles

Effect of long-term tafamidis treatment on health-related quality of life in patients with transthyretin amyloid cardiomyopathy.

To evaluate the effect of long-term tafamidis treatment on health-related quality of life (HRQoL) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) enrolled in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension (LTE) study. We examined change from baseline in Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) and clinical summary (KCCQ-CS) scores in patients who received tafamidis meglumine 80 mg for 30 months in ATTR-ACT and tafamidis (meglumine 80 mg or bioequivalent free acid 61 mg) for 30 months in the LTE study, and in patients who received placebo for 30 months in ATTR-ACT and tafamidis for 30 months in the LTE study. In ATTR-ACT, 176 and 177 patients were randomized to tafamidis 80 mg and placebo, respectively. Patients who continuously received tafamidis had a 6- to 7-point reduction in least squares (LS) mean (standard error) KCCQ-OS and KCCQ-CS scores at month 30 (-6.25 [1.53] and -7.48 [1.39]), with little or no further decline over the next 30 months (-5.92 [1.77] and -9.21 [1.88] at month 60). Patients who received placebo in ATTR-ACT had a 20-point reduction in LS mean KCCQ-OS and KCCQ-CS scores at month 30 (-19.60 [1.94] and -19.90 [2.01]), but the decline slowed after initiating tafamidis (-24.70 [3.04] and -25.30 [3.36] at month 60). Tafamidis reduced HRQoL decline in patients with ATTR-CM. Patients continuously treated with tafamidis for 60 months demonstrated stabilized HRQoL. In patients who initially received placebo in ATTR-ACT, tafamidis reduced the decline in HRQoL during the LTE study.

Cost-Effectiveness Analysis of Empagliflozin for Treatment of Patients With Heart Failure With Reduced Ejection Fraction in the United States.

In the EMPEROR-Reduced trial (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction), empagliflozin plus standard of care reduced the composite of cardiovascular death or hospitalization for heart failure versus standard of care in adults with heart failure with reduced ejection fraction. This analysis investigated the cost-effectiveness of the 2 regimens from the perspective of US payors. A Markov cohort model was developed based on Kansas City Cardiomyopathy Questionnaire Clinical Summary Score quartiles and death. Transition probabilities between health states, risk of cardiovascular/all-cause death, hospitalization for heart failure and adverse events, treatment discontinuation, and health utilities were estimated from trial data. Medicare and commercial payment rates were combined for treatment acquisition, acute event management, and disease management. An annual discount rate of 3% was used. Empagliflozin plus standard of care yielded 18% fewer hospitalizations for heart failure and 6% fewer deaths versus standard of care over a lifetime, providing cost-offsets while adding 0.19 life years and 0.19 quality-adjusted life years at an incremental cost of $16 815/patient. The incremental cost-effectiveness ratio was $87 725/quality-adjusted life years gained. Results were consistent across payors, subpopulations, and in deterministic sensitivity analyses. In probabilistic sensitivity analyses, empagliflozin plus standard of care was cost-effective in 3%, 62%, and 80% of iterations at thresholds of $50 000, $100 000, and $150 000/quality-adjusted life years. Empagliflozin plus standard of care may prevent hospitalizations for heart failure, extend life, and increase quality-adjusted life years for patients with heart failure with reduced ejection fraction at an acceptable cost for US payors.

Percutaneous Transcatheter Closure of a Post-device Residual Aorta-pulmonary Window

Introduction The aortopulmonary window (APW) is a rare congenital cardiac anomaly in which there is incomplete separation of the pulmonary artery and aorta. Percutaneous transcatheter closure is possible in a specific subset of APWs only, and surgery remains the mainstay of therapy. Clinical summary We report a rare case of percutaneous device closure of post-device residual APW in a 32-month-old baby who had residual shunt post the device closure at two months of age. Discussion Transcatheter closure of an aortopulmonary window is an effective and safe procedure for specific anatomic defects.

Effects of SGLT2 inhibitors on cardiac function and health status in chronic heart failure: a systematic review and meta-analysis

PurposeNumerous clinical studies have explored sodium–glucose cotransporter 2 inhibitor (SGLT2i) in patients with chronic heart failure (CHF), with or without type 2 diabetes mellitus (T2DM), and SGLT2i were proved to significantly reduce CHF hospitalization, cardiovascular death, cardiovascular mortality, all-cause mortality and myocardial infarction in patients with or without T2DM. However, only a limited few have investigated the effects of SGLT-2i on HF disease-specific health status and cardiac function. This meta-analysis aims to assess the effects of SGLT2i on disease-specific health status and cardiac function in CHF patients.MethodsA comprehensive search was conducted of trials by searching in PubMed, EMBASE, CENTRAL, Scopus, and Web of Science, and two Chinese databases (CNKI and Wanfang), Clinical Trials (http://www.clinicaltrials.gov) were also searched.ResultsA total of 18 randomized controlled trials (RCTs) involving 23,953 participants were included in the meta-analysis. The effects of SGLT2 inhibitors were compared with control or placebo groups in CHF with or without T2DM. The SGLT2 inhibitors group exhibited a significant reduction in pro b-type natriuretic peptide (NT-proBNP) levels by 136.03 pg/ml (95% confidence interval [CI]: −253.36, − 18.70; P = 0.02). Additionally, a greater proportion of patients in the SGLT2 inhibitors group showed a ≥ 20% decrease in NT-proBNP (RR = 1.45, 95% CI [0.92, 2.29], p = 0.072). However, no statistically significant difference was observed for the effects on B-type natriuretic peptide (BNP). The use of SGLT-2 inhibitors led to a noteworthy improvement in LVEF by 2.79% (95% CI [0.18, 5.39];P = 0.036). In terms of health status, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) and 6-minute walk distance, SGLT2 inhibitors led to a significant improvement in KCCQ clinical summary (KCCQ-CS) score (WMD = 1.7, 95% CI [1.67, 1.73], P < 0.00001), KCCQ overall summary (KCCQ-OS) score (WMD = 1.73, 95% CI [0.94, 2.52], P < 0.00001), and KCCQ total symptom (KCCQ-TS) score (WMD = 2.88, 95% CI [1.7, 4.06], P < 0.00001). Furthermore, the occurrence of KCCQ-CS and KCCQ-OS score increases ≥ 5 points had relative risks (RR) of 1.25 (95% CI [1.11, 1.42], P < 0.00001) and 1.15 (95% CI [1.09, 1.22], P < 0.00001), respectively. Overall, SGLT2 inhibitors increased the 6-minute walk distance by 23.98 m (95% CI [8.34, 39.62]; P = 0.003) compared to control/placebo from baseline.ConclusionsThe SGLT2 inhibitors treatment offers an effective strategy for improving NT-proBNP levels, Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance in CHF with or without T2DM. These findings indicate that SGLT2i improve cardiac function and health status in CHF with or without T2DM, and provide valuable guidance for clinicians making treatment decisions for patients with CHF.

A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events.Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.

A Quality Improvement Project of Acute Red Eye Consultations in Primary Care: Improving the Identification of Red Flags.

Aim The acute red eye or conjunctival injectionis the most common ophthalmic presentation in primary care.The aim of this audit was to improve red eye consultations by increasing the number of red flag features documented in the history of patients. Method The National Institute of Clinical Excellence (NICE) Clinical Knowledge Summary (CKS) outlines red flag features, which should be documented for an acute red eye consultation. Two interventions were implemented to attempt to improve consultations. The first involved creating a template in the Egton Medical Information Systems. The second involved training doctors in the recognition of red flag features and identifying sight-threatening conditions. Red eye consultations and red flag features documented were recorded in the two months before and after the interventions. Results All documentation of red flag features assessed in this project increased post intervention. However, lateralisation, visual changes, and eye pain were commonly asked prior to the intervention and did not show a statistically significant difference. They showed an increase from 90% (19/21) to 100% (19/19), 71% (15/21) to 84% (16/19), and 67% (14/21) to 79% (15/19), respectively. After the interventions, significant increases in asking about headaches (14% (3/21) to 74% (14/19), pupil changes (5% (1/19) to 58% (11/19)), and method of injury (high velocity 10% (2/21) to 84% (16/19), foreign body 14% (3/21) to 84% (16/19), chemical 10% (2/21) to 84% (16/19) were observed (p<0.05). Photophobia inquiries also significantly increased (14% (3/19) to 79% (15/19), P<0.05). Conclusion The number of red flag features identified and documented for acute red eye consultations increased with the introduction of an online template and a teaching session.

Biobanking in the hospital of a multidisciplinary research medical center as a potential for a wide research range. Part II. Specifics and first results of developing a described collection of biomaterial

In connection with the development of genetic and other types of research in translational medicine, collections containing a significant number of biospecimens and large data sets are required. Since in-depth examination of patients is most often carried out during hospitalization, the creation of collections based on electronic medical records (EMR) data is promising. In this regard, the project "Total biobanking in the hospital of the National Medical Research Center for Therapy and Preventive Medicine" was initiated, aimed at total biobanking of blood and related products from patients in inpatient departments and the creation of a unified system that combines information on biosamples, clinical and other types of data.Aim. To describe the collection of biospecimens collected within the project "Total biobanking in the hospital of the National Medical Research Center for Therapy and Preventive Medicine" for August 2023, and to analyze the process of biospecimen description.Material and methods. Recruitment of patients is carried out on the basis of inpatient departments of the National Medical Research Center for Therapy and Preventive Medicine, only if the patient signs informed consent. After blood is taken, the biomaterial enters the biobank, where sample preparation and storage is carried out, as well as data about each biosample is entered into a special FreezerPRO system. At the same time, clinical data about the patient is collected using EMR, which are combined in the Medialog medical information system.Results. A special software for data exchange between the medical information system and the biobank has been developed, which combines information about patients entering the Medialog medical information system and the FreezerPro biospecimen management system, which contains detailed information about biospecimens. As of August 25, 2023, biomaterial from 3996 patients was collected, which was accompanied by a detailed clinical summary. In particular, data is available on diagnoses (for 100% of patients), laboratory test data (100%), paraclinical data, in particular, electrocardiography (100%), echocardiography (76,8%), 24-hour Holter monitoring (59,8%), esophagogastroduodenoscopy (27,3%), etc. The most common diseases were hypertension (76,0%), atherosclerosis (69,9%), coronary artery disease (52,9%), arrhythmias (50,6%), diabetes (19,2%). In addition, 25,0% of patients had prior stenting.Conclusion. Total biobanking within the hospital of a multidisciplinary research medical center allows for the rapid and high-quality collection of biomaterial and related data. A collection of biospecimens with comprehensive and detailed clinical annotations has been collected. A primary analysis of the collection was carried, which showed that it can be used for a wide range of studies.

SOLUBLE GUANYLATE CYCLASE STIMULATORS IN HEART FAILURE WITH PRESERVED EJECTION FRACTION: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Aims: We conducted a systemic review and meta-analysis to evaluate the therapeutic efficacy and safety of soluble guanylate cyclase (sGC) stimulators in patients with heart failure with preserved ejection fraction (HFpEF). Methods : We systematically searched PubMed, Embase, and Cochrane Library databases for original randomized controlled trials comparing sGC stimulators with placebo in HFpEF patients. A random-effects model was applied to evaluate the mortality, quality of life, and drug-related adverse events. This meta-analysis is registered in PROSPERO under the number CRD42023457382. Results : We included five studies involving 1,600 HFpEF patients. Comprehensively, the combined risk ratio (RR) for mortality was not significant (RR [95% CI] = 1.44 [0.71 to 2.91], P = 0.31). Furthermore, there were no statistically significant differences in the Kansas City Cardiomyopathy Questionnaire results, including the clinical summary score (weighted mean difference [WMD] [95% CI] =0.32 [-7.38 to 8.02], P = 0.94) and the overall summary score (WMD [95% CI] = -0.87 [-8.87 to 7.14], P = 0.83). Similarly, there was no significant improvement in the 6-minute walk distance (WMD [95% CI] = -6.22 [-18.56 to 6.12], P = 0.32). In addition, drug-related adverse events were more common in patients treated with sGC stimulators (RR [95% CI] = 1.63 [1.25-2.14], P < 0.05). Conclusion : Oral sGC stimulators do not significantly improve mortality outcomes, functional capacity, and quality of life in HFpEF patients but are associated with increased drug-related adverse events. Therefore, we should consider using sGC stimulators in HFpEF patients carefully.

Effect of Mavacamten in Women Compared With Men With Obstructive Hypertrophic Cardiomyopathy: Insights From EXPLORER-HCM.

Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy). A prespecified post hoc analysis of sex from the blinded, randomized EXPLORER-HCM trial of mavacamten versus placebo in symptomatic patients with obstructive HCM was performed. Baseline characteristics were compared with t tests for continuous variables (expressed as mean values) and χ2 tests for categorical variables. Prespecified primary, secondary, and exploratory end points and echocardiographic measurements from baseline to end of treatment (week 30) were analyzed with ANCOVA for continuous end points and a generalized linear model with binomial distribution for binary end points, with adjustment for each outcome's baseline value, New York Heart Association class, β-blocker use, and ergometer type. At baseline, women (n=102) were older (62 years versus 56 years; P<0.0001), had lower peak oxygen consumption (16.7 mL·kg-1·min-1 versus 21.3 mL·kg-1·min-1; P<0.0001), were more likely to be assigned New York Heart Association class III (42% versus 17%; P<0.0001), had worse health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 64 versus 75; P<0.0001), and had higher baseline plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (1704 ng/L versus 990 ng/L; P=0.004) than men (n=149). After 30 weeks of mavacamten treatment, similar improvements were observed in women and men in the primary composite end point (percentage difference on mavacamten versus placebo, 22% versus 19%, respectively; P=0.759) and in the secondary end points of change in postexercise left ventricular outflow tract gradient (-42.4 mm Hg versus -33.6 mm Hg; P=0.348), change in peak oxygen consumption (1.2 mL·kg-1·min-1 versus 1.6 mL·kg-1·min-1; P=0.633), and percentage achieving ≥1 New York Heart Association class improvement (41% versus 28%; P=0.254). However, women had greater improvement in health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 14.8 versus 6.1; P=0.026) and in the exploratory end point of NT-proBNP levels (-1322 ng/L versus -649 ng/L; P=0.0008). Although at baseline women with symptomatic obstructive HCM enrolled in EXPLORER-HCM were older and had worse heart failure and health status than men, treatment with mavacamten resulted in similar improvements in the primary and most secondary EXPLORER-HCM end points and greater improvements in health status and NT-proBNP. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.

Accelerometer-measured physical activity in patients with heart failure and reduced ejection fraction: determinants and relationship with patient-reported health status

Abstract Background Accelerometer-measured physical activity is an increasingly used endpoint in heart failure (HF) trials. Purpose We aimed to investigate the determinants of accelerometer-measured physical activity and to establish the minimal clinically important difference (MCID). Methods Post-hoc analysis of the Empire HF trial, including stable outpatients with HF with reduced ejection fraction (HFrEF). Physical activity was quantified as average accelerometer counts per minute (CPM) with higher values representing higher activity. Associations between activity level and important clinical variables [age, sex, body mass index, N-terminal pro-brain natriuretic peptide, left ventricular ejection fraction (LVEF), atrial fibrillation, and anemia], as well as patient-reported health status (Kansas City Cardiomyopathy Questionnaire, KCCQ) were assessed. Results Complete data were available in 180 (95%) patients (86% male, mean age 65 years, mean LVEF 30%). Baseline median physical activity level was 1318 CPM (Q1-Q3 1111–1585). At baseline, age and anemia were independently associated with activity level (β-coefficients: -10 CPM per year age increase [95% CI -16 to -5.1], p = 0.00015, and -126 CPM for presence of anemia [95% CI -9.1 to -244], p = 0.035). Moreover, a significant independent association was observed between activity level and all KCCQ summary scores (β-coefficient point estimates of 3.7, 4.6, and 4.9 CPM, all p&amp;lt;0.02). For 12-week changes, only the KCCQ-clinical summary score (CSS) was associated with activity level, with a mean increase of 17.5 CPM [95% CI 1.5 to 34.0], p = 0.032, for every clinically relevant 5-point increase in KCCQ-CSS, corresponding to the MCID. Conclusion In patients with HFrEF, high age and anemia were independently associated with lower accelerometer-measured physical activity. Moreover, clinically relevant 5-point increases in Kansas City Cardiomyopathy Questionnaire clinical summary scores at 12 weeks were associated with an increase of 17.5 activity counts per minute, thus representing the minimal clinically important difference.Table 1.Baseline characteristicsFigure 1

Relationship between change in Kansas City Cardiomyopathy Questionnaire scores and outcomes in patients with HFrEF

Abstract Background Although a 5-point change in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores is widely recognized as representing a clinically meaningful change in symptoms and quality of life, it is not known how changes KCCQ scores relate to risk of hospitalization and death. Purpose To evaluate how changes in KCCQ summary scores relate to subsequent risk of hospitalization and death in a large cohort of patients with heart failure and reduced ejection fraction (HFrEF). Methods We used individual patient data from 3 HFrEF trials (ATMOSPHERE, PARADIGM-HF, and DAPA-HF) to examine the association between changes in KCCQ summary scores between baseline and 8-months and the subsequent risk of cardiovascular death or HF hospitalization, using Cox-proportional hazard models. Change in score was categorized as very small (&amp;gt;0 &amp;lt;5), small (&amp;gt; = 5 &amp;lt;10), moderate (&amp;gt; = 10 &amp;lt;20), and large (&amp;gt; = 20) points. We examined the KCCQ total symptom score (KCCQ-TSS), KCCQ clinical summary score (KCCQ-CSS), and KCCQ overall summary score (KCCQ-OSS). Results Among 15,892 participants with HFrEF, 1403 patients (8.8%) had a large deterioration in KCCQ score, 1688 (10.6%) a moderate deterioration, 1442 (9.1%) a small deterioration, 1527 (9.6%) a very small deterioration, and 2326 (14.6%) no deterioration. Conversely, 1836 patients (11.6%) had a very small improvement, 1732 (10.9%) a small improvement, 2202 (13.9%) a moderate improvement, and 1736 (10.9%) a large improvement. Patients with larger changes in KCCQ scores were older and more often female and had lower baseline summary scores and worse heart failure characteristics. Worsening heath status i.e., decrease in the KCCQ-TSS, was associated with a higher risk of the composite outcome (and each of its components), as well as all-cause mortality (Figure 1). On the contrary, improvements in KCCQ-TSS were not associated with better clinical outcomes (Figure 1). The findings were similar for 4-month changes of KCCQ-TSS, and changes in other KCCQ scores (KCCQ-CSS and KCCQ-OSS) at both 4 and 8-months. Conclusion Decreases (deterioration) in KCCQ summary scores during follow-up were associated with worse outcomes in patients with HFrEF but no association was seen between improvement in KCCQ scores and outcomes. These findings have potential implications for the interpretation of the effect of treatment on KCCQ scores.

Abstract 15228: Impact of Gender and Left Ventricular Ejection Fraction on Health-Related Quality of Life and Its Change in Patients With Heart Failure

Introduction: Health-related quality of life (HRQoL) is an important part in managing patients with heart failure (HF). However, the influence of clinical factors on HRQoL in HF remains limited. Hypothesis: This study aimed to examine HRQoL changes based on gender and left ventricular ejection fraction (LVEF) among patients with HF. Methods: A total of 199 patients hospitalized for acute HF (mean age, 71±14 years; men:women=119:80; mean LVEF=42±16) were enrolled in a prospective way from Jan 2022 to Jan 2023. Baseline and 4-month follow-up Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were assessed. Patients were categorized into 4 subgroups: Group 1, women with LVEF≥50% (n=37); Group 2, men with LVEF≥50% (n=26); Group 3, women with LVEF&lt;50% (n=43); Group 4, and men with LVEF&lt;50% (n=93). Results: Women demonstrated lower KCCQ clinical and overall summary scores than men at baseline (p=0.003, 0.004, respectively) and 4-month follow-up (p=0.029, 0.038, respectively) after adjusting for age and body mass index. In addition, these scores tended to be lower in patients with LVEF ≥50% than those with LVEF &lt;50% at both baseline and follow-up (all p&lt;0.05). When we assessed KCCQ scores according to group, group 1 showed the lowest KCCQ overall summary score (KCCQ-OS: 36.9 [IQR 22.9-49.8], p=0.004) and clinical summary score (KCCQ-CS: 37.8 [IQR: 24.5-51.1], p=0.001). Also, the scores for physical limitation, symptom frequency, symptom burden, social limitation, self-efficacy scale, and total symptom score were lowest in Group 1 (all p&lt;0.05). Although HRQoL improved across all groups, the follow-up KCCQ-OS and KCCQ-CS scores remained lowest in Group 1 (KCCQ-OS: 54.0 [IQR 44.3-64.4], p=0.026; KCCQ-CS: 56.5 [IQR: 45.0-63.9], p=0.031). Conclusions: Among patients with HF, women with LVEF≥50% reported significantly worst HRQoL even after HF treatment, suggesting more attention should be paid to HRQoL in managing this specific population during HF treatment.

Abstract 13640: Baseline Kidney Function and the Effects of Dapagliflozin on Health Status in Heart Failure: A Pooled Patient-Level Analysis From DFEINE-HF and PRESERVED-HF

Background: Sodium-glucose co-transport-2 (SGLT2) inhibitors have been shown to reduce clinical events and improve health status (symptoms, function, and quality of life) in patients with HF across the range of EF. Baseline kidney dysfunction is common in HF, complicates HF management, and is strongly linked to worse health status. Aim: The study objective was to assess whether the treatment effects of dapagliflozin on health status vary based on baseline eGFR. Methods: Patient-level data were pooled from the DEFINE-HF (N = 263 participants with EF &lt; 40%) and PRESERVED-HF trials (N = 324 participants with EF &gt; 45%). Both were double-blind, randomized trials of dapagliflozin vs. placebo, enrolling participants with NYHA class II or higher and elevated natriuretic peptides. The primary endpoint for this analysis was Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CCS) at 12 weeks. Interaction of dapagliflozin effects on KCCQ-CCS by baseline eGFR (mL/min/1.73m 2 ) was assessed as categorical (i.e., eGFR &lt;60 vs. &gt; 60) and continuous variables. Results: Across both trials there were 583 (99.3%) participants with available baseline eGFR. The median (25 th , 75 th ) eGFR was 59 (46,77). Dapagliflozin improved KCCQ-CSS at 12 weeks (placebo-adjusted difference, +5.0 points, 95% Confidence Interval [CI] 2.6-7.5; p-value &lt;0.001), and this was consistent in participants with an eGFR &gt; 60 (+6.0 points, 95% CI 2.4-9.7; p=0.001) and &lt;60 (+4.1 points, 95% CI 0.5-7.7; p=0.025) (p-interaction = 0.46). The benefits of dapagliflozin on KCCQ-CSS were robust across eGFR when modeled continuously (p-interaction = 0.46) ( Figure ). There was no heterogeneity of treatment effects when analyzing other KCCQ domains based on eGFR categorically or continuously (all p-interaction = NS). Conclusion: Treatment with dapagliflozin for 12 weeks led to significant and consistent improvements in health-related quality of life in patients with HF across a wide range of eGFRs.

Abstract 14176: Cardiac Structure and Function in Relation to Health-Related Quality of Life in Heart Failure Patients With Preserved Ejection Fraction: Results From the PARAGON-HF Study

Background: Health-related quality of life (HRQL) is reduced in patients with heart failure with preserved ejection fraction (HFpEF). However, the extent to which HRQL outcomes are related to cardiac structure and function in patients with HFpEF is not well understood. Methods: We examined the association between baseline echocardiographic measures and longitudinal Kansas City Cardiomyopathy Questionnaire (KCCQ) measures in patients with HFpEF in the PARAGON-HF trial using longitudinal regression models adjusted for age, sex, baseline KCCQ score, randomization, and other important clinical confounders. Results: Among 1,094 patients with baseline KCCQ data at randomization and a baseline echocardiogram within 6 months of enrollment, the mean age was 74 years and 53% were women. Over 3 years, 78% completed KCCQ measures at baseline, 12, 24, and 36 months. Missing values for non-survivors (n=116) were imputed as zero to avoid survival bias. Posterior wall thickness, septal E/e’, and right ventricular (RV) end diastolic area were negatively associated with the KCCQ Overall Summary Score, and a similar pattern of associations was observed for the KCCQ Clinical Summary Score (Table). Pulmonary artery systolic pressure was additionally negatively associated with the KCCQ Total Symptom Score. Notably, left ventricular (LV) size, septal wall thickness, LV ejection fraction, LV strain, and left atrial size were not significantly associated with longitudinal changes in KCCQ. Conclusion: In patients with HFpEF, increased LV posterior wall thickness, elevated LV filling pressure, elevated pulmonary pressure, and RV enlargement - together suggestive of more advanced diastolic dysfunction - are associated with a decline in KCCQ scores and may influence future worsening of quality of life.

Mavacamten for Obstructive Hypertrophic Cardiomyopathy With or Without Hypertension: Post-Hoc Analysis of the EXPLORER-HCM Trial

BackgroundHypertension (HTN) is common in patients with hypertrophic cardiomyopathy (HCM), but its effect on the treatment of left ventricular outflow tract (LVOT) obstruction is undefined. Although elevated systolic blood pressure (SBP) may impact dynamic LVOT gradients, its response to cardiac myosin inhibition is unknown. ObjectivesIn a post hoc exploratory analysis of the EXPLORER-HCM trial (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy), the authors examined the characteristics of patients with obstructive HCM and HTN and the associations between HTN, SBP, and the response to mavacamten treatment of LVOT obstruction. MethodsPatients were stratified by baseline history of HTN and mean SBP during 30-week treatment with mavacamten or placebo. The study estimated treatment differences and evaluated HTN and SBP groups by treatment interaction. Analysis of covariance was used to model changes in continuous endpoints, and a generalized linear model was used for binary endpoints. ResultsHTN was present in 119 of 251 patients (47.4%), including 60 receiving mavacamten and 59 receiving placebo. Patients with HTN vs no HTN were older (63.4 vs 54.0 years; P < 0.001), had higher SBP (134 ± 15.1 mm Hg vs 123 ± 13.8 mm Hg; P < 0.001), more comorbidities, and lower peak oxygen consumption (19 ± 3 vs 20 ± 4 mL/kg/min; P = 0.021). Patients with HTN had similar NYHA functional class (NYHA functional class II, 72% vs 73%), Valsalva LVOT gradients (72 ± 34 mm Hg vs 74 ± 30 mm Hg), Kansas City Cardiomyopathy Questionnaire–Clinical Summary Scores (70.6 ± 18.8 vs 68.9 ± 23.1), and NT pro–B-type natriuretic peptide levels (geometric mean 632 ± 129 pg/mL vs 745 ± 130 pg/mL). Mavacamten-treated patients had improvement in all primary, secondary, and exploratory endpoints regardless of HTN status or mean SBP. ConclusionsThe clinical benefits of mavacamten in symptomatic, obstructive HCM were similar in patients with and without HTN, despite differences in baseline characteristics. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy [EXPLORER-HCM]; NCT03470545)

Clinical features and mutational analysis of X-linked agammaglobulinemia patients in Malaysia.

Bruton's tyrosine kinase (BTK) is a cytoplasmic protein involved in the B cell development. X-linked agammaglobulinemia (XLA) is caused by mutation in the BTK gene, which results in very low or absent B cells. Affected males have markedly reduced immunoglobulin levels, which render them susceptible to recurrent and severe bacterial infections. Methods: Patients suspected with X-linked agammaglobulinemia were enrolled during the period of 2010-2018. Clinical summary, and immunological profiles of these patients were recorded. Peripheral blood samples were collected for monocyte BTK protein expression detection and BTK genetic analysis. The medical records between January 2020 and June 2023 were reviewed to investigate COVID-19 in XLA. Twenty-two patients (from 16 unrelated families) were molecularly diagnosed as XLA. Genetic testing revealed fifteen distinct mutations, including four splicing mutations, four missense mutations, three nonsense mutations, three short deletions, and one large indel mutation. These mutations scattered throughout the BTK gene and mostly affected the kinase domain. All mutations including five novel mutations were predicted to be pathogenic or deleterious by in silico prediction tools. Genetic testing confirmed that eleven mothers and seven sisters were carriers for the disease, while three mutations were de novo. Flow cytometric analysis showed that thirteen patients had minimal BTK expression (0-15%) while eight patients had reduced BTK expression (16-64%). One patient was not tested for monocyte BTK expression due to insufficient sample. Pneumonia (n=13) was the most common manifestation, while Pseudomonas aeruginosa was the most frequently isolated pathogen from the patients (n=4). Mild or asymptomatic COVID-19 was reported in four patients. This report provides the first overview of demographic, clinical, immunological and genetic data of XLA in Malaysia. The combination of flow cytometric assessment and BTK genetic analysis provides a definitive diagnosis for XLA patients, especially with atypical clinical presentation. In addition, it may also allow carrier detection and assist in genetic counselling and prenatal diagnosis.

Best evidence summary of prevention strategies for pressure injury in adult hospitalized burn patients

Objective: To summarize the best evidence of prevention strategies for pressure injury in adult hospitalized burn patients. Methods: A bibliometric approach was used. Systematic searches were carried out to retrieve the published evidence of prevention strategies for pressure injury in adult hospitalized burn patients in the official websites of relevant academic organizations such as International Society for Burn injury, American Burn Association, and Japanese Dermatology Association, National Pressure Injury Advisory Panel, European Pressure Injury Advisory Panel, Pan Pacific Pressure Injury Alliance International Guidelines Website, foreign language databases such as UpToDate, BMJ Best Practice, MedSci, Joanna Briggs Institute Evidence-Based Practice Database, Cochrane Library, Web of Science, Embase, and PubMed, and Chinese databases such as China Biology Medicine disc, China National Knowledge Infrastructure, Wanfang Database, and China Clinical Guidelines Library. The literature types include clinical decision-making, evidence summary, guidelines, systematic review, and expert consensus. The search time was till February 21st, 2023. Two researchers independently screened the literature and evaluated the quality, and other researchers extracted and graded the evidence according to the topic. Results: A total of 10 papers were included, including 6 evidence summaries, 3 guidelines, and 1 expert consensus, all with high literature quality. After extracting evidence and classifying, 27 pieces of best evidences were summarized from three aspects, including prevention training and supervision, risk assessment, and prevention measures of pressure injury. Conclusions: A total of 27 pieces of best evidences of prevention strategies for pressure injury in adult hospitalized burn patients were summarized from 3 aspects. Medical workers can follow the best evidence and give personalized prevention strategies according to the specific condition of adult hospitalized burn patients to reduce the incidence of pressure injury.

Efficacy and safety of mavacamten in treatment of hypertrophic cardiomyopathy: a systematic review and meta-analysis.

This meta-analysis was performed to assess the efficacy and safety of mavacamten in patients with hypertrophic cardiomyopathy. A search was conducted using PubMed, Cochrane, and Scopus up to August 2022 for randomized studies reporting our pre-specified outcomes. It was observed that mavacamten significantly improved New York Heart Association class (p<0.009), Clinical Summary Score of theKansas City Cardiomyopathy Questionnaire(p=0.02), post-exercise left ventricular outflow tractgradient (p<0.00001), functional end point (p=0.05), and lowered septal reduction therapyrates (p<0.00001). However, there were no significant differences in the ≥1 severe adverse events, ≥1 treatment-emergent adverse events, left ventricular volume index, left ventricularfilling pressure, left ventricular end-diastolic volumeindex, and peak oxygen uptake(pVO2). Future large-scale trials are required to confirm our results and determine the long-term benefits and risks of mavacamten use in these patients.

Effect on the Quality of Life of Patients with Heart Failure and Reduced/Preserved Ejection Fraction Using Sacubitril/Valsartan.

Heart failure (HF) management has markedly improved, but a clinically meaningful improvement in functional capacity and quality of life is perhaps more important for patients than living longer. This study aimed to review the improvement in quality of life with sacubitril/valsartan in patients with HF and reduced/preserved ejection fraction (EF) from prospective clinical trials. PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) and prospective cohort studies published from inception to July 2021. A total of 6 clinical trials and 16854 patients with HF were included. The primary outcome was the change from baseline in KCCQ clinical summary score. The secondary outcomes were scores in other domains of KCCQ, the occurrence of serious adverse events (AEs), and overall mortality. P-values <0.05 were considered statistically significant. Treatment of sacubitril/valsartan showed significantly higher KCCQ-CSS compared to the control (WMD=0.975, 95% CI: 0.885, 1.064, p<0.001; I2=94.8%, pheterogeneity<0.001). A significant decrease in the mortality rate was observed in the sacubitril/valsartan group compared to the control group (RR=0.895, 95%CI:0.831, 0.965, p=0.004; I2=43.6%, pheterogeneity=0.150). Nevertheless, no significant reduction in the occurrence of serious AEs was found among HF patients treated with sacubitril/valsartan compared to the control group (RR=0.950, 95%CI: 0.879, 1.027, p<0.001; I2=68.1%, pheterogeneity=0.024). Our study demonstrated that sacubitril/valsartan might significantly improve the HRQL compared to other treatments according to the results in KCCQ-CSS and some subdomains in the KCCQ index during the follow-up in patients with HF.

Effect of Mavacamten on Chinese Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy

Mavacamten has shown clinical benefits in global studies for patients with obstructive hypertrophic cardiomyopathy (oHCM), but evidence in the Asian population is lacking. To evaluate the safety and efficacy of mavacamten compared with placebo for Chinese patients with symptomatic oHCM. This phase 3, randomized, double-blind, placebo-controlled clinical trial was conducted at 12 hospitals in China. Between January 4 and August 5, 2022, patients with oHCM and a left ventricular outflow tract (LVOT) gradient of 50 mm Hg or more and New York Heart Association (NYHA) class II or III symptoms were enrolled and received treatment for 30 weeks. Patients were randomized 2:1 to receive mavacamten (starting at 2.5 mg once daily) or placebo for 30 weeks. The primary end point was change in Valsalva LVOT peak gradient from baseline to week 30. Left ventricular outflow tract gradients and left ventricular ejection fraction (LVEF) were assessed by echocardiography, while left ventricular mass index (LVMI) was determined by cardiac magnetic resonance imaging. Analysis was performed on an intention-to-treat basis. A total of 81 patients (mean [SD] age, 51.9 [11.9] years; 58 men [71.6%]) were randomized. Mavacamten demonstrated a significant improvement in the primary end point compared with placebo (least-squares mean [LSM] difference, -70.3 mm Hg; 95% CI, -89.6 to -50.9 mm Hg; 1-sided P < .001). Similar trends were demonstrated for resting LVOT peak gradient (LSM difference, -55.0 mm Hg; 95% CI, -69.1 to -40.9 mm Hg). At week 30, more patients receiving mavacamten than placebo achieved a Valsalva LVOT peak gradient less than 30 mm Hg (48.1% [26 of 54] vs 3.7% [1 of 27]), less than 50 mm Hg (59.3% [32 of 54] vs 7.4% [2 of 27]), and NYHA class improvement (59.3% [32 of 54] vs 14.8% [4 of 27]). Greater improvements were also observed with mavacamten regarding the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (LSM difference, 10.2; 95% CI, 4.4-16.1), N-terminal pro-B-type natriuretic peptide level (proportion of geometric mean ratio, 0.18; 95% CI, 0.13-0.24), high-sensitivity cardiac troponin I level (proportion of geometric mean ratio, 0.34; 95% CI, 0.27-0.42), and LVMI (mean difference, -30.8 g/m2; 95% CI, -41.6 to -20.1 g/m2). Safety and tolerability were similar between mavacamten and placebo. No patients experienced LVEF less than 50%. Mavacamten significantly improved Valsalva LVOT gradient vs placebo for Chinese patients. All secondary efficacy end points were also improved. Mavacamten was well tolerated with no new safety signals. This study supports the efficacy and safety of mavacamten in diverse populations, including Chinese patients. ClinicalTrials.gov Identifier: NCT05174416.