In 2023 the European Society of Cardiology published its first comprehensive guideline on cardiomyopathies. OpenAlex has already logged more than 2,100 citations to that single document, a pace that puts it among the fastest-accelerating clinical papers of 2024. The guideline itself is not the story. The story is what it quietly codified: a drug class that did not exist in human medicine four years ago is now written into the standard of care, and the competitive landscape behind it is moving faster than the trade press has noticed.

Cardiac myosin inhibitors blunt the contractile protein at the center of hypertrophic cardiomyopathy, the most common inherited heart disease. Mavacamten, developed by MyoKardia and acquired by Bristol Myers Squibb for $13.1 billion in 2020, became the first approved drug in the class in April 2022. The ESC 2023 guideline upgraded it to a Class IIa recommendation for symptomatic obstructive HCM. That editorial decision, buried in a 127-page document, changed the economics of every follow-on asset in the pipeline.

Look at what is chasing mavacamten right now.

Cytokinetics received a US grant in July 2025 on methods for treating HCM using aficamten (US 12,370,179), alongside 2024 and 2025 patents on the synthesis process itself (US 11,932,631, US 12,247,024). The Phase 3 SEQUOIA-HCM readout in late 2024 put aficamten on the FDA review path. Between 2023 and 2026 the ClinicalTrials.gov registry logs twenty-five new mavacamten or aficamten studies, spanning pediatric and adolescent populations, real-world effectiveness in China, India, Japan, Korea, and Canada, and four pregnancy surveillance protocols. The indication is expanding on contact with the market.

The fast-follower is Chinese. Hansoh Pharma’s HRS-1893 entered Phase 2 in August 2024 (NCT06516068), added a second Phase 2 in non-obstructive HCM in February 2025 (NCT06816251), and launched a Phase 3 in August 2025 (NCT07021976). One company, three parallel trials, in twelve months. The ESC guideline provided the regulatory scaffolding that made the pipeline worth building.

A stranger thread is running in parallel. Sotagliflozin, Lexicon’s dual SGLT1/SGLT2 inhibitor, started a Phase 3 in both obstructive and non-obstructive HCM in September 2024 (NCT06481891). A Korean group enrolled a Phase 4 of enavogliflozin in non-obstructive HCM a month later (NCT06580717). An investigator-initiated study in December 2024 is testing pan-SGLT inhibitors in the same population (NCT06433050). A drug class originally developed for type 2 diabetes, recycled into heart failure with reduced ejection fraction, then into heart failure with preserved ejection fraction, is now being tested against a structural cardiomyopathy. That recycling has no market niche without the ESC guideline creating the clinical definitions that drug developers can target.

A third mechanism is queuing up. NCT06555237, a Phase 2 launched in August 2024, is testing MEK inhibitors in HCM caused by RASopathies, the developmental syndromes where RAS-MAPK signaling is dysregulated. Oncology pharmacology is arriving in structural cardiology by way of a pediatric genetics indication. Five years ago that sentence would read like nonsense.

The device side is moving too. Edwards Lifesciences holds a 2024 grant on a system for HCM and left ventricular outflow tract obstruction (US 12,029,650). Three separate RF ablation catheter patents, from Tau Medical, the Asan Foundation, and China’s Fourth Military Medical University (US 12,279,810, US 12,193,726), describe interventional alternatives to the surgical septal myectomy that cardiac surgeons have performed since the 1970s. A gene therapy program out of Sorbonne University and UKE Hamburg-Eppendorf holds a 2023 US grant on AAV-based cardiomyopathy vectors (US 11,773,408), extending a 2019 filing from the same consortium.

The 2023 ESC cardiomyopathies guideline is not alone on the citation-acceleration list. ESC guidelines for heart failure (focused update), acute coronary syndromes, and endocarditis — all 2023 vintage — sit in the same top bracket. Four major clinical guidelines from one society, published within six months, all absorbed into the evidence base at record pace. The ACVIM feline cardiomyopathy consensus statement from 2020 also appears on the leaderboard, a reminder that the same pathology is being defined across species.

For an R&D director the practical question is how much commercial room remains in a landscape that already contains two myosin inhibitors, at least three SGLT variants, a MEK inhibitor, a trimetazidine analog, and two mechanical device approaches in human trials for the same disease. For a corp dev scout the question is whether Cytokinetics stays independent, and whether the Chinese Phase 3 alters the acquisition calculus. For a regulatory watcher the question is what the FDA does when the ESC and the AHA start disagreeing on class placement for a genuinely new mechanism. Those are not the questions the guideline authors were answering. But the document they wrote is now the reference text that every commercial decision in this space points back to.

—

Method note. The signal is the ratio of 2024 to 2023 citations for each paper, computed from an OpenAlex monthly citation dump refreshed in early 2026, filtered to works published between 2018 and 2023 with at least fifty citations in 2024. The top 100 fastest-growing papers by that ratio form the leaderboard. The ESC 2023 cardiomyopathies guideline published late in 2023, which inflates the ratio because the 2023 denominator covers only a partial year. The stronger read is absolute pace: OpenAlex’s lifetime citation count for this guideline is 2,120 as of the early-2026 dump, which is fast for a clinical practice document barely past its first anniversary. Patent identifiers were verified against the USPTO grant text index; trial identifiers are current ClinicalTrials.gov records. No text-level link between the guideline and the assets named here was computed. The connection is inferential and should be confirmed against the guideline before any investment decision.