Early detection and monitoring of transthyretin amyloid cardiomyopathy
Early detection and monitoring of transthyretin amyloid cardiomyopathy
The research of Alwin Tubben sheds light on a previously underdiagnosed heart disease: transthyretin amyloid cardiomyopathy (ATTR-CM). This condition is caused by a misfolded protein that builds up in the heart, causing it to stiffen and ultimately leading to fatal heart failure. ATTR-CM can be hereditary, caused by a genetic mutation that can affect people at any age (ATTR-variant), or it can occur later in life for unknown reasons, known as wild-type ATTR-CM (ATTRwt-CM). This disease, particularly ATTRwt-CM, is far more prevalent than previously thought, estimated to affect between 1 in 2,000 and 10,000 people. Its prevalence is many times higher in specific patient groups, such as those with heart failure with a preserved ejection fraction (HFpEF) and patients with the heart valve disease aortic stenosis. Currently, cardiac amyloidosis can be accurately diagnosed with a combination of tests: a fat biopsy, a blood test, and a nuclear scan called bone scintigraphy.
In our studies, we showed for the first time in the Netherlands that ATTRwt-CM affects 13% of patients with HFpEF and 10% of those undergoing a common heart valve procedure (TAVI) for severe aortic stenosis. These findings highlight the importance of early detection, as new treatments are most effective when initiated in the early stages of the disease.
However, a major challenge is that most current markers for ATTRwt-CM reflect a more advanced disease stage. To address this, we aimed to find novel methods for earlier identification, including the use of protein biomarkers found in the blood. We successfully identified two promising biomarkers, IDUA and DCN, for the detection of ATTRwt-CM. We also found that a common cardiac imaging test, cardiac magnetic resonance (CMR), was not a reliable tool for early diagnosis in our patient group.
Another diagnostic challenge is to distinguish ATTRwt-CM in co-existence with blood disorder, monoclonal gammopathy of unknown significance (MGUS)from a more rapidly progressing condition, light-chain amyloidosis (AL-CM). While our study found a high prevalence (26%) of MGUS in patients with ATTRwt-CM in the Netherlands as well, we were unable to find a specific biomarker to differentiate it from AL-CM.
The final focus of this thesis was on a critical gap in current clinical practice: monitoring a patient's response to treatment. While current methods primarily focus on disease progression, we successfully developed a novel quantification method using an advanced nuclear imaging technique, [123I]-MIBG SPECT/CT. This method can quantify the exact disease burden, which allows for better comparison on follow-up scans and holds potential for future clinical use.
Ultimately, our research provides promising new insights and tools that contribute to the ongoing effort to detect this silent heart disease sooner, laying the groundwork for future advancements in patient care.