Advanced cardiac MRI guides treatment for stiff heart syndrome

For the first time, doctors can measure the effectiveness of chemotherapy for “stiff heart syndrome”, using an advanced form of cardiac magnetic resonance imaging (MRI). Researchers at the National Amyloidosis Centre of University College London (UCL) have been developing and refining the non-invasive technique for the past 10 years.

Light-chain cardiac amyloidosis, also known as stiff heart syndrome, is a condition in which the heart muscle thickens due to the build up of amyloid fibrils throughout the heart. In early stages, the pumping function is typically preserved, but eventually the heart muscle can no longer efficiently pump blood and pressure starts to build up, leading to shortness of breath and fluid retention in the lungs and limbs. Without treatment, this can rapidly lead to heart failure and death.

Chemotherapy is the first-line treatment to reduce amyloid protein, but until now there has been no way to efficiently measure its therapeutic effect. A patient’s haematological response to chemotherapy is generally evaluated using measurements of serum free light chains (FLC), while echocardiography parameters and serum concentration of brain natriuretic peptides are currently the reference standards for assessing cardiac organ response. But these indirect biological markers do not directly measure cardiac amyloid burden.

The new imaging procedure combines cardiovascular MR (CMR) with extracellular volume (ECV) mapping to measure the presence and, importantly, the amount of amyloid protein in the heart. This approach can determine whether the chemotherapy is effective in triggering cardiac amyloid regression, information that will help guide better, more timely, treatment strategies for patients.

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Principal investigator Ana Martinez-Naharro and colleagues assessed the ability of CMR with ECV mapping to measure changes in response to chemotherapy in a study following 176 patients with light-chain cardiac amyloidosis for two years. They report their findings in the European Heart Journal.

The newly diagnosed patients, who were enrolled in a long-term prospective observational study at the National Amyloidosis Centre, underwent a series of assessments. These included N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements and CMR with T1 mapping and ECV measurements at baseline and at six, 12 and 24 months after the start of chemotherapy with bortezomib. The team also measured FLC monthly to assess haematological response.

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When combined with results of blood tests, the imaging exams revealed that almost 40% of patients had a substantial reduction in amyloid deposition following chemotherapy. “The scans and data made available using this technique, combined with correlating data from indirect markers that currently exist, gave us the information to both see the amount of amyloid protein and also the regression in amyloid during the course of chemotherapy treatments,” says Martinez-Naharro.

Senior author Marianna Fontana, of the UCL Division of Medicine, recommends that the MRI technique should now be employed immediately to diagnose and assess all cases of light-chain cardiac amyloidosis. “By developing ECV mapping for 1.5 T MR scanners, we hope that its use can be made available to more patients. The aim would be to use these scans routinely for all patients with the disease to help improve patient survival, which is very poor in patients who do not respond to treatment,” she explains.

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In this study cohort, only patients who achieved complete haematological response or very good partial response experienced regression in cardiac amyloid deposits following chemotherapy. The study also showed that, after adjusting for known predictors, changes in ECV could predict patient outcome, including death, as early as six months into treatment.

“Future management of cardiac amyloidosis is likely to be a multidimensional approach, where haematological, NT-proBNP response and CMR response will have a different role at different time points. The combination of these markers will depict a comprehensive clinical picture that could help clinicians to better tailor chemotherapy treatment in each individual patient,” the researchers conclude, noting that that the ability to measure changes in cardiac amyloid load over time could also provide an endpoint for early-state drug development and dose ranging.