8/8 Read the full study in Nature Medicine here: www.nature.com/articles/s41...
Press release from @MGBResearchNews: www.massgeneralbrigham.org/en/about/new...
Press release from @dzhk_germany : dzhk.de/newsroom/akt...
7/8 Huge thanks to co-lead Nich Marston, co-authors: Giorgio Melloni, S. Jurgens, F. Kamanu, Yi-Pin Lai, @joelramo.bsky.social, I.Raz & S.Wiviott, senior authors Patrick Ellinor, Marc Sabatine, and Christian Ruff. Incredible effort #UKEHamburg , #TIMIStudyGroup @mgbresearch.bsky.social
6/8 Historically, finding a CMP variant just meant giving bad prognostic news. Genetic screening could identify asymptomatic patients who may benefit from early, preventative SGLT2i therapy. This needs to be studied prosp. and in larger numbers!
5/8 This yields a 13.0% absolute risk reduction in carriers compared to a 1.0% ARR in non-carriers. Notably, 82% of carriers had no prior HF diagnosis. In this asymptomatic subgroup, the absolute risk of HHF was reduced by 12.8%.
4/8 Dapagliflozin reduced HHF by 82% in CMP variant carriers (vs. 30% in non-carriers). Treatment brought the absolute rate of HHF down to 3.1%, effectively neutralizing the excess genetic risk and mirroring the rate seen in non-carriers.
3/8 Baseline risk is high. In the placebo arm, 16% of CMP variant carriers were hospitalized for HF compared to 3.5% of non-carriers. Carrying a P/LP variant translated to an 8-fold increased relative risk for incident HHF.
2/8 We analyzed WES data from 12,685 patients with T2D randomized to dapagliflozin vs. placebo in the DECLARE-TIMI 58 trial. Over a median 4.2-year follow-up, we identified 121 carriers of pathogenic/likely pathogenic (P/LP) variants for DCM, HCM, or ARVC.
1/8 SGLT2 inhibitors are a cornerstone of HF prevention, but do they work in patients with a genetic predisposition to cardiomyopathy? Out in @NatureMedicine, our latest from the @TIMI_Study_Group evaluates dapagliflozin in carriers of rare CMP variants.
Dr. James Pirruccello identified new genetic factors that help explain why some people develop aortic stenosis by analyzing advanced heart imaging and genetic data from 60,000 healthy participants from the UK Biobank. www.nature.com/articles/s41...