Background: Valsartan has previously been shown to attenuate cardiac remodeling among individuals with early-stage sarcomeric hypertrophic cardiomyopathy (HCM), a condition characterized, in part, by increased cardiomyocyte size. Cardiac magnetic resonance (CMR) imaging parameters, such as late gadolinium enhancement (LGE), are associated with disease progression and outcomes in HCM, but whether valsartan influences these parameters remains uncertain. Methods: In this prespecified CMR substudy of the international, multicenter, phase 2 VANISH (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) trial, we evaluated treatment effects of valsartan versus placebo on cardiac structure and function, including indexed extracellular volume (iECV), indexed intracellular volume (iICV; reflecting cell size or number), and LGE. Between-group differences in CMR parameters from baseline to 2 years were evaluated using multivariable mixed effects models. Results: Overall, 137 (77%) VANISH participants (mean age 23±10 years; 37% female; 97% White) had CMR imaging available at baseline and 2 years. Baseline characteristics and CMR parameters were well-balanced between the treatment arms. Baseline non-indexed ECV and ICV (available at baseline and year 2 in 52 participants) were 32±7% and 68±7%, respectively. Among those with detectable LGE (n=37; 27%), the median [IQR] global LGE mass was 10 [2-28] grams. Between baseline and 2 years, iICV was significantly reduced with valsartan vs. placebo (between-group difference, -5.0 mL/m 2 , 95% CI -9.7 to -0.4; P =0.032) ( Figure ). Valsartan was also associated with improved left ventricular end-diastolic volume index vs. placebo (between-group difference, +3.3 mL/m 2 , 95% CI 0.4 to 6.2; P =0.027); no significant between-group differences were observed for other CMR parameters, including iECV and global LGE mass. Conclusions: These findings provide important mechanistic insights into the effect of valsartan in early-stage HCM, showing potential benefits on myocardial intracellular volume. These findings support and extend those of the primary VANISH trial, stressing the need for further research efforts to identify cellular mechanisms of valsartan on HCM progression.
Background: Real-world evidence is critical to identify treatment gaps and inform healthcare service design, but contemporary anti-obesity medication (AOM) use patterns are sparsely reported. Aims: To describe the prevalence of obesity/overweight, evidence-based obesity-related conditions (ORCs), and AOM use among eligible patients, with a focus on cardiovascular disease (CVD). Methods: In this cross-sectional analysis of the multicenter Mass General Brigham healthcare system spanning 2018-2022, we identified all adult patients eligible for AOM (BMI 27-29.9 kg/m 2 with ≥1 ORC or BMI ≥30 kg/m 2 ). The prevalence of ORCs was ascertained using administrative codes and available EHR data. Prescription of FDA-approved AOM by BMI category, number of ORCs, number of key CVD risk factors, and the presence of prior MACE were also evaluated. Results: Of 2,922,522 individuals who met inclusion criteria, 998,234 (34%) were eligible for AOM (mean age, 49 years; 53% female). Of these, 30%, 41%, 18%, and 11% had a BMI (kg/m 2 ) of 27-29.9, 30-34.9, 35-39.9, and ≥40, respectively. Prior metabolic/bariatric surgery was seen in 2.3%. Musculoskeletal disorders (54%), dyslipidemia/hyperlipidemia (35%), and hypertension (32%) were the most common ORCs, with ≥2 ORCs observed in 58%. Prescription of any FDA-approved AOM was observed in only 1.2% of all eligible patients. Liraglutide 3.0 mg (58% of all AOM) was the most prescribed AOM. AOM prescriptions increased modestly with higher BMI, ORC burden, and number of CVD risk factors ( Figure ). Among those with prior MACE (11%), 1.5% (1.0% if without T2DM) were prescribed FDA-approved AOM. Conclusions: Although more than 1 in 3 contemporary patients in a large healthcare system are eligible by guidelines and FDA labeling, AOM prescription remains exceedingly low, even among high-risk persons with severe obesity and established CVD. Novel care delivery pathways are needed to accelerate closure of these considerable implementation gaps.
Albuminuria (urine albumin-to-creatinine ratio [UACR] ≥30 mg/g) and estimated glomerular filtration rate (eGFR) constitute the basis of contemporary kidney disease staging, and are independently associated with HF onset and progression. 1 ME Grams Coresh J Matsushita K et al. Writing Group for the CKD Prognosis ConsortiumEstimated Glomerular Filtration Rate, Albuminuria, and Adverse Outcomes: An Individual-Participant Data Meta-Analysis. JAMA. 2023; 330: 1266-1277 Crossref Scopus (15) Google Scholar , 2 Stevens PE Ahmed SB Carrero JJ et al. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work GroupKDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024; 105: S117-S314 Scopus (11) Google Scholar , 3 Butler J Packer M Siddiqi TJ et al. Efficacy of Empagliflozin in Patients With Heart Failure Across Kidney Risk Categories. J Am Coll Cardiol. 2023; 81: 1902-1914 Crossref Scopus (9) Google Scholar , 4 Khan MS Shahid I Anker SD et al. Albuminuria and Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2023; 81: 270-282 Crossref PubMed Scopus (19) Google Scholar As such, assessment of these complementary domains is important in clinical and research efforts involving the HF population. However, because UACR has been infrequently assessed in HF outcomes trials, generalizability of trial-level kidney risk to real-world HF populations remains uncertain.
Background: Code selection is crucial to the accuracy and reproducibility of studies using administrative data, however a comprehensive assessment of coding trends for major cardiac diagnoses and procedures is lacking. We aimed to evaluate trends in administrative code utilization for major cardiac diagnoses and procedures, and adherence to required methodological practices in cardiac research using the National Inpatient Sample (NIS). Methods: In this observational study of 445 articles, ICD-9-CM codes corresponding to acute myocardial infarction (AMI), heart failure, atrial fibrillation, percutaneous coronary intervention, and coronary artery bypass grafting were collected and analyzed. The NIS was used to compare the number of hospitalizations between the most frequently encountered AMI case definitions. Key elements were abstracted from each article to evaluate adherence to required methodological practices. Results: Variation in code utilization was observed for each diagnosis and procedure assessed, and the number of unique case definitions published per year increased throughout the study period (P < 0.001), driven largely by the significant increase in articles per year (P < 0.001). Off-target codes were observed in 39 (8.8%) studies. Upon reintroduction into the NIS for 2008-2012, the most commonly encountered case definitions for AMI were found to yield significantly different estimates of AMI hospitalizations and hospitalization trends over time. Three hundred and ninety-nine articles (84%) did not adhere to one or more required research practices. Overall adherence was superior for publications in higher-impact journals (P = 0.002). Conclusions: Substantial variation in code selection exists for major cardiac diagnoses and procedures, and non-adherence to methodological standards is widespread. These data have important implications for the accuracy and generalizability of analyses using the NIS.
Introduction: Code selection is crucial to the accuracy and reproducibility of studies using administrative data, however a comprehensive assessment of coding trends for major cardiac diagnoses and procedures is lacking. Hypothesis: Given the absence of consensus guidelines for administrative code utilization, heterogeneity in code selection for major cardiovascular diagnoses and procedures will be uncovered. Methods: We queried PubMed, CINAHL, Scopus, Medline, and the HCUP Publication Search from inception through March 1st, 2018 for all publications using the National Inpatient Sample (NIS), featuring a primary focus on the heart. ICD-9-CM codes reported for acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG) were collected and analyzed for accuracy and consistency. All studies were also evaluated for adherence to required methodological practices as per previously reported methods. Results: Of 2637 articles identified, 445 were included in the observational analysis. 399 articles (84%) did not adhere to one or more research practices required by the AHRQ, however overall adherence was superior for publications in higher impact journals ( P = 0.0019). Heterogeneity in code utilization was observed for each diagnosis and procedure assessed, with up to 37 unique case definitions reported for HF and PCI. Nonspecific codes were included in 39 (8.8%) studies, and coding heterogeneity increased throughout the study period ( P trend < 0.001 for all cardiac diagnoses and procedures). Coding schema endorsed by national-level clinical guidance documents were infrequently represented, reported in only 8.9% and 1.3% of AMI and HF articles, respectively. Upon reintroduction into the NIS for the period of 2008 to 2012, selected unique case definitions for AMI were found to yield significantly different estimates of AMI incidence. Conclusions: Substantial heterogeneity in code selection exists for major cardiac diagnoses and procedures, with important implications for the accuracy and generalizability of analyses using the NIS. Further efforts are required to establish consensus protocols to ensure consistency in code utilization.
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