Credits - Section Writer: [[Dr. Om J Lakhani]] - Section Editor: [[Dr. Om J Lakhani]] Support us: 1. [Support you by Becoming a YouTube member (Click here)](https://www.youtube.com/channel/UC6zQSf7dLDqfQOeM4mNUBTQ/join).  - Premium Membership- Download PDF version of Notes, Get ad free video and more - Consultant Membership- Above plus Download Powerpoint presentation of the notes 2. Support us by purchasing our book - Click here for more details: - [[Volume 1- THE BEST OF NOTES IN ENDOCRINOLOGY BOOK SERIES]] - [[Volume 2- THE BEST OF NOTES IN ENDOCRINOLOGY - DIABETES SPECIAL]] 3. For more such updates follow our WhatsApp Channel: https://whatsapp.com/channel/0029VaFyQnfHbFUz0LVdBO3h ----- - Q. What is the [[STEP-HFpEF DM Trial]] ? - Ref: Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Treppendahl MB, Verma S, Jensen TJ. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. New England Journal of Medicine. 2024 Apr 6. - New trial published in NEJM in April 2024: - Background: The article discusses a clinical trial focusing on patients with obesity-related heart failure with preserved ejection fraction (HFpEF) who also have type 2 diabetes. There are few existing treatments targeting this patient group. - Methods: The trial randomly assigned participants to receive either semaglutide (2.4 mg) or a placebo once weekly for 52 weeks. The primary endpoints were the change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and body weight. - Results: - KCCQ-CSS Improvement: Semaglutide group saw an average increase of 13.7 points versus 6.4 points for the placebo group. - Weight Loss: Semaglutide group had an average percentage weight loss of 9.8% compared to 3.4% in the placebo group. - Secondary Endpoints: Semaglutide improved the 6-minute walk distance by an average of 14.3 meters more than placebo and showed a significant reduction in C-reactive protein levels. - Safety: Fewer serious adverse events were reported in the semaglutide group compared to the placebo group. - Conclusions: Semaglutide led to significant improvements in heart failure–related symptoms, physical limitations, and weight loss compared to placebo, making it a promising treatment option for patients with obesity-related HFpEF and type 2 diabetes. - Clinical Implications: The results support semaglutide as an effective treatment for reducing symptoms and physical limitations in patients with HFpEF and type 2 diabetes, also noting its positive impact on weight and exercise capacity. - Q. What is Kansas City Cardiomyopathy Questionnaire clinical summary score ? - The Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) is a patient-reported outcome tool used to assess the health status of individuals with heart failure. Here are some key points about KCCQ-CSS: - Purpose: It measures the physical limitations, symptoms, social limitations, and quality of life related to heart failure. - Components: The clinical summary score specifically combines the total symptom score (frequency and severity of symptoms) and physical limitation score (impact on mobility and physical activity). - Scoring: Scores range from 0 to 100, with higher scores indicating fewer symptoms and physical limitations, thus reflecting a better heart failure-related health status. - Sensitivity to Change: The KCCQ-CSS is sensitive to clinical changes over time, making it useful for monitoring the progression of heart failure or the response to treatment in clinical trials and practice. - Validation: The KCCQ is a validated tool that has been widely used in clinical research and practice to provide a quantitative measure of the patient's perspective on their heart failure management and outcomes. - Clinical Use: It helps clinicians to evaluate the effectiveness of treatments and to make informed decisions about patient care based on changes in their reported health status. - The KCCQ-CSS is particularly valuable because it captures data directly from the patients about how heart failure impacts their daily lives, providing a comprehensive picture of treatment impact beyond clinical and biomarker assessments. - Q. What was the diagnostic criteria for HFpEF used for enrollment in this study ? - Documented heart failure: Participants needed a confirmed diagnosis of heart failure. - Left ventricular ejection fraction: The ejection fraction had to be at least 45%. - Additional evidence: Participants must have had one of the following: - Elevated left ventricular filling pressures, - Elevated natriuretic peptide levels combined with echocardiographic abnormalities, or - Hospitalization for heart failure within 12 months before screening, plus echocardiographic abnormalities or ongoing treatment with diuretics. - Q. Were patients in this trial on SGLT2 inhibitors also ? - Yes, patients in the trial were also on SGLT2 inhibitors. - The study reported that 32.8% of participants were receiving SGLT2 inhibitors at the start of the trial. - Q. What was the median NT-pro-BNP level for patients enrolled in the trial ? - The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) level for patients enrolled in the trial was approximately 493 pg/ml. - This value represents the overall median level for the participants at baseline, reflecting the typical heart stress or failure status in the cohort studied. - Q. Was there a reduction in NT-pro-BNP levels seen ? - Yes, there was a reduction in NT-proBNP levels observed among participants receiving semaglutide. - Specifically, the semaglutide group experienced a mean percentage reduction in NT-proBNP levels of 23.2%, compared to a reduction of 4.6% in the placebo group. - This reduction in NT-proBNP levels suggests that semaglutide had a beneficial effect on cardiac stress, which is indicative of improved heart failure management among the trial participants. - Q. What was the mean BMI of the participants ? - The mean body mass index (BMI) of the participants in the trial was 36.9 kg/m2. This indicates that the average participant was classified as obese, which aligns with the study's focus on obesity-related heart failure with preserved ejection fraction (HFpEF) in patients with type 2 diabetes. - Q. What was the importance of reduction of the CRP levels ? - Overall, the decrease in CRP levels underscores the anti-inflammatory benefits of semaglutide, highlighting its role in improving cardiovascular health and reducing the burden of heart failure in patients with type 2 diabetes. Ref: Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, Kitzman DW, Møller DV, Treppendahl MB, Verma S, Jensen TJ. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. New England Journal of Medicine. 2024 Apr 6.