HCM is characterised by enlargement of the left ventricular and septal wall of the heart muscles. This affects heart muscle (myocardium) contraction and the blood flow at rest and on exertion, resulting in dysfunctional electrical activity in the heart. As a result, people with HCM get arrhythmias resulting in sudden cardiac death (SCD). BIG-HEART is an EU-funded project that aims to elucidate the disease mechanisms and treatment options for HCM. Project researchers collected myocardial tissue samples from both HCM-inflicted and non-affected individuals for identification of genetic mutations. Standardised protocols and approvals were obtained for reproducibility and uniformity of results. The three different HCM disease genes identified for study were ACTC, MYBPC3 and TNNT2. Positron emission tomography (PET) studies in HCM and non-HCM patients showed impaired blood circulation and myocardial fibrosis in HCM patients. Direct correlation was found between HCM gene mutations and adverse remodelling of the heart. Three-dimensional (3D) visualisation of the myocytes and electron microscope (EM) images of HCM and non-HCM samples identified haploinsufficiency as a possible cause of HCM. Haploinsufficiency occurs when only a single functional copy of a gene exists and which cannot produce enough gene product (e.g. protein) and leads to disease. Innovative antiarrhythmic drugs such as ranolazine were tested on HCM myocytes and found to be effective in controlling HCM symptoms. An ACTC E99K mouse model was developed to investigate Ca2+ sensitivity, messenger ribonucleic acid (Mrna) level changes and altered muscle cell function. RNA-based therapy of genetic diseases such as spliceosome-mediated RNA trans-splicing (SmaRT) were identified as promising therapeutic options. For a more complete understanding of HCM, mouse models were generated with mutations in ACTC, MYBPC3, TNNT2 genes for the BIG-HEART study. The study findings have been published in scientific journals, leaflets, a quarterly newsletter and emails. The project website (http://www.big-heart.eu) is a portal for the public and healthcare professionals. The findings from this study will have a huge impact on developing therapies for HCM that afflict about a million people in the EU.