Hypertrophic cardiomyopathy (HCM), a genetic heart condition characterized by the thickening of the heart muscle, affects approximately 1 in 500 people across Europe. This inherited disorder can lead to serious complications including sudden cardiac death, heart failure, arrhythmias, and the need for life-saving interventions like implantable cardioverter-defibrillators or even heart transplants. For years, clinicians have relied on established risk calculators, such as the European Society of Cardiology's HCM Risk-SCD model, which primarily focuses on sudden cardiac death prediction using factors like left ventricular wall thickness, age, family history, and nonsustained ventricular tachycardia. However, these tools fall short in forecasting broader adverse outcomes, leaving many patients and their families in uncertainty.

Researchers at the University of Oxford have now changed the landscape with a groundbreaking study that integrates advanced cardiac magnetic resonance (CMR) imaging—commonly known as heart scans—with simple blood tests. This Oxford-led effort, part of the international Hypertrophic Cardiomyopathy Registry (HCMR), demonstrates how these non-invasive tools can significantly refine risk assessment, offering a more holistic view of patient prognosis. Conducted across 44 specialized centers, with 22 in Europe, the study underscores the collaborative strength of European academic institutions in advancing cardiovascular science.

🔬 The HCMR Study: Methodology and European Collaboration

The HCMR study represents one of the largest prospective investigations into HCM, enrolling nearly 2,700 patients from diverse backgrounds. Participants underwent standardized protocols including detailed clinical histories, genotyping, blood sampling for biomarkers like N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T, and contrast-enhanced CMR scans to evaluate heart structure, function, and fibrosis (scarring).

Follow-up averaged seven years, during which researchers tracked major adverse cardiac events—a composite endpoint encompassing sudden cardiac death or equivalent, heart failure hospitalization, sustained ventricular tachycardia, and cardiac transplantation or left ventricular assist device implantation. European sites played a pivotal role, with Oxford's Radcliffe Department of Medicine leading alongside centers like London Chest Hospital and Glenfield Hospital in Leicester. This pan-European network ensured robust data diversity, reflecting real-world HCM presentations across the continent.

The rigorous, quality-controlled approach—funded in part by the UK's National Institute for Health and Care Research (NIHR) Biomedical Research Centre at Oxford—highlights how university-led consortia can drive precision medicine. By pooling resources from institutions in the UK, Germany, Italy, and beyond, the study exemplifies the European Research Area's commitment to tackling inherited diseases.

Figure illustrating the 22 European HCMR sites, emphasizing Oxford's central coordination role.

Patient Demographics and Baseline Characteristics

• Median age: 52 years
• 53% male
• Prevalent sarcomere gene mutations in 40%
• Baseline symptoms mild in most, but 15% had prior heart failure

Breakthrough Insights from Cardiac MRI

CMR emerged as a game-changer, revealing subtle abnormalities invisible to echocardiography. Key features linked to higher risk included:

• Presence and extent of late gadolinium enhancement (LGE), indicating myocardial fibrosis—a hallmark of arrhythmogenic substrate.
• Increased left ventricular mass and abnormal wall thickness patterns.
• Reduced left ventricular ejection fraction (LVEF), signaling systolic dysfunction.

Patients with significant LGE (over 10% of myocardium) faced a hazard ratio of approximately 2.5 for adverse events, independent of traditional factors. This imaging modality, widely available in European university hospitals, allows for precise quantification, far surpassing 2D echo limitations. Oxford's imaging expertise, honed through NIHR-funded programs, was instrumental in standardizing protocols across sites.

The Role of Blood Biomarkers

Blood tests provided complementary prognostic power. Elevated NT-proBNP, a marker of cardiac stress, strongly predicted both composite events and sudden death, with levels above 365 pg/mL doubling risk. High-sensitivity troponin T, indicating myocyte injury, further refined stratification.

These assays are cost-effective and routine, making the model practical for Europe's national health systems like the NHS. The study's biomarker data, analyzed at Oxford labs, opens doors for serial monitoring, potentially guiding therapy timing.

Comparative Model Performance

Model	C-Index for Composite Endpoint
Traditional ESC HCM Risk-SCD	0.65
New Integrated Model (CMR + Biomarkers + History)	0.78

The enhanced model outperformed standards, improving net reclassification by 25% for high-risk patients.

Clinical Translation: Transforming European Practice

For the estimated 1.4 million Europeans living with HCM, this means personalized care. High-risk individuals could receive prophylactic ICDs earlier, while low-risk ones avoid unnecessary interventions. The findings align with calls from the European Society of Cardiology for multimodal stratification, potentially influencing 2026 guideline updates.Explore ESC HCM resources.

University clinics in Oxford, Leicester, and beyond are poised to implement CMR routinely, supported by EU-funded imaging networks.

Oxford University's Leadership in Cardiovascular Research

Professor Stefan Neubauer, Oxford's imaging theme lead, spearheaded this effort, building on decades of HCM work. "Our results show these measurements provide powerful risk predictors," he noted. Collaborator Professor Hugh Watkins emphasized the "landmark achievement" for MRI in HCM.

Backed by NIHR Oxford BRC, this exemplifies how UK universities anchor European excellence, attracting talent and funding.

Broader European Academic Impact

With 22 European sites contributing, universities from Germany to Italy bolstered data validity. This fosters cross-border trials, vital amid rising HCM diagnoses—prevalence stable at 0.2% but underdiagnosed in rural areas.

Implications extend to training: cardiology fellows at Oxford now prioritize CMR, shaping next-gen researchers.

Challenges and Future Horizons

Challenges include CMR access in smaller centers and cost. Yet, AI enhancements from Oxford pilots promise automation.

Ongoing HCMR follow-up and EU Horizon projects will validate long-term. Gene therapies, trialed at European unis, could pair with refined risk tools.

Stakeholder Perspectives

• Patients: Empowered by precise forecasts.
• Clinicians: Evidence for guideline advocacy.
• Researchers: Blueprint for biomarker-imaging integration.

This Oxford-led advance cements Europe's forefront in cardiac genetics, promising safer lives for HCM patients continent-wide.