Cardiology Know&Manage

Precise molecular diagnosis

• Reduced diagnostic delay and patient burden
• Genotype-guided therapy and surveillance
• Risk stratification and prognosis assessment
• Predictive family screening and early intervention in asymptomatic relatives
• Pharmacogenetic optimisation of cardiovascular therapy

Patient–related findings

• Unexplained ventricular arrhythmias, recurrent syncope or aborted sudden cardiac death (SCD)
• Abnormal ECG findings suggestive of inherited arrhythmia syndrome
• Imaging findings suggestive of cardiomyopathy, particularly in children and young adults
• Heritable thoracic aortic aneurysm or dissection, or bicuspid aortic valve
• Heart defects where a genetic aetiology is suspected, particularly syndromic or familial forms
• Premature coronary artery disease
• Patients receiving cardiovascular polypharmacy where metaboliser status may affect drug efficacy or safety

Family history–related findings

• Positive family history of an inherited cardiovascular disease or characteristic clinical phenotype
• SCD in a first- or second-degree relative
• First-degree relative of an index case once a causal genetic variant has been identified (predictive testing)

This selection highlights common cardiovascular genetic findings and does not replace comprehensive clinical evaluation. For detailed diagnostic pathways and management recommendations, please refer to current (ESC) Guidelines and ESC cardiovascular genomics consensus statements.

Interpretation of genetic findings requires correlation with the patient’s clinical phenotype, family history, and other relevant clinical information. Variants are classified according to the five-tier ACMG/AMP framework, namely pathogenic, likely pathogenic, variant of uncertain significance, likely benign or benign. Where appropriate, gene- and disease-specific criteria are also considered, in line with ESC cardiovascular genomics recommendations. Results are reported according to clinically relevant variant categories:

Pathogenic or likely pathogenic variant

One or more genetic variants known or likely to be disease-causing may be identified. This can confirm or support the molecular diagnosis and inform risk stratification, clinical management, and family testing.

Variant of uncertain significance (VUS)

One or more genetic variants with currently insufficient evidence to determine whether they are disease-causing or benign may be identified. Clinical management should remain guided by the patient’s phenotype and family history. Re-evaluation over time may support variant reclassification. Predictive testing in relatives based solely on a VUS is not recommended.

No clinically relevant variant identified

No disease-associated variants are detected in the analysed genes. This does not exclude a genetic cause. Clinical management should remain guided by the patient’s phenotype and family history, and reanalysis may be considered over time.