The Role of Cardiac Imaging in Deep Phenotyping Patients with Cardiomyopathy

Cardiomyopathy is a major cause of heart failure (HF) and can be caused by a range of genetic and acquired factors. Genetic causes account for approximately 25% of idiopathic dilated cardiomyopathy (DCM), with Titin truncating variants (TTNtv) the most common cause. Obesity, present in up to half of HF patients, can be a primary cause of cardiac dysfunction and has also been identified as an important disease modifier in TTNtv-related DCM. However, the mechanisms linking obesity and cardiomyopathy need further investigation. The first project within this thesis utilised advanced CMR imaging techniques to refine phenotyping of obesity-related cardiomyopathy, TTNtv, and their combination. A prospective study was conducted phenotyping 25 subjects with obesity before and after bariatric surgery, and comparisons made with 24 normal-weight controls. Notably, obesity-related cardiomyopathic changes were only partially reversible, despite significant weight loss. The second project studied 29 TTNtv-positive individuals (17 TTNtv carriers without DCM, and 12 individuals with TTNtv-related DCM) and 29 healthy controls. All individuals underwent deep cardiac phenotyping. Distinct cardiovascular features were discovered in early-onset and established TTNtv-related DCM, including the novel discovery of distinct atrial abnormalities. The third project explored metabolomic and lipidomic changes in 85 subjects (TTNtv, obesity and healthy controls). Notably, TTNtv carriers without phenotypic DCM, already exhibited distinct maladaptive metabolic alterations, findings further amplified in established DCM. Obesity also modifies the metabolic phenotype of TTNtv carriers without DCM and was associated with increased muscle catabolism and impaired vascular function. TTNtv carriers without DCM also demonstrate compensatory lipidomic adaptations, which shift towards detrimental remodelling upon progression to DCM, also amplified by obesity. Taken together, the research contained within this thesis describes novel deep- phenotypic CMR, metabolomic and lipidomic changes in TTNtv-related DCM and obesity, further elucidating on the complex genotype-phenotype interaction in these conditions.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2026

Author dc:creator

• Pereira Kessler Iglesias, Cassia

• Cardiomyopathy
• Obesity
• CMR
• Titin
• TTNtv
• Metabolomics
• Heart Failure
• anzsrc-for: 320101 Cardiology (incl. cardiovascular diseases)

Statement dc:rights

• embargoed access
• CC BY 4.0

Licence

• http://purl.org/coar/access_right/c_f1cf
• https://creativecommons.org/licenses/by/4.0/

Language dc:language

en

Identifier

https://doi.org/10.26190/unsworks/32348

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/107922