Expert perspectives on diagnosis and monitoring of transthyretin amyloid cardiomyopathy in Asia
02 Dec 2022
byDr. Chan Wan Xian
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a significantly underdiagnosed, life-threatening condition with a heterogeneous clinical presentation. Recently, clinical recommendations to diagnose and monitor ATTR-CM patients in Asia were published. Dr Chan Wan Xian, Cardiologist at the Asian Heart & Vascular Centre, Gleneagles Hospital, Mount Elizabeth Hospitals, and Parkway East Hospital, Singapore, reviews these guidelines and shares practical tips for diagnosing and assessing ATTR-CM patients.
ATTR-CM diagnosis often delayed
ATTR-CM is a devastating condition that has a serious impact on morbidity and mortality. If left untreated, patients often progress to end-stage heart failure, with a poor prognosis. Early diagnosis and treatment are essential for improving prognosis before prolonged amyloid deposition, which eventually leads to symptomatic organ dysfunction. [Orphanet J Rare Dis 2022;17:262]
Regrettably, diagnosis of ATTR-CM is often delayed because of physician- and disease-related reasons, including fragmented knowledge among different specialists and subspecialists, shortage of centres and specialists dedicated to disease management, the perceived rarity of the condition, as well as intrinsic phenotypic and genotypic heterogeneity. [Circ Heart Fail 2019;12:e006075]
“The diagnosis of cardiac amyloidosis relies on a high index of clinical suspicion. However, presenting symptoms and signs can be nonspecific and vague. As such, the condition is underdiagnosed, and diagnosis is often delayed. “To counter this, awareness and understanding of cardiac amyloidosis among physicians and healthcare professionals need to be increased,” said Chan.
Red flags for ATTR-CM
The spectrum of clinical presentations in patients with ATTR-CM obliges all clinicians to be aware of common disease patterns. Table 1 summarizes possible red flags that can be identified from an initial physical examination and assessment of patient history, which may prompt screening of cardiac amyloidosis. Red flags may support a suspicion of ATTR‐CM and lead to subsequent referral to a cardiologist and/or neurologist. [Clin Cardiol 2022;45:898-907]
“Cardiac conditions such as heart failure, abnormal ECG, or abnormal heart rhythm warrant further diagnostic evaluation to ascertain the underlying cause of clinical presentation. Other nonspecific symptoms should be considered in the context of overall clinical risks and signs, as well as family history of hereditary heart conditions,” explained Chan.
“Based on clinical experience, the presenting clinical symptoms and signs of ATTR-CM patients in Asia are similar to those in Europe and the US,” she added.
Diagnostic pathway for ATTR-CM
The diagnostic pathway for ATTR‐CM begins with the suspicion of amyloidosis, followed by initiation of the cardiac workup to assess the patient’s ECG and echocardiography or cardiac magnetic resonance imaging (CMR), if available. If the findings suggest possible cardiac amyloidosis, screening for monoclonal protein followed by scintigraphy or biopsy are recommended. If no monoclonal protein is detected and a diagnosis of AL cardiac amyloidosis is excluded, radionuclide scintigraphy alone without endomyocardial biopsy, can be used to diagnose ATTR-CM. [Clin Cardiol 2022;45:898-907]
The panel recommendations for suspicion and diagnosis of ATTR-CM in Asia are outlined in Table 2.
Treatment response and disease progression
Currently, the only therapy approved for ATTR-CM by the Singapore Health Sciences Authority is tafamidis, a selective transthyretin stabilizer. Randomized clinical trials have shown that tafamidis reduces all-cause mortality and cardiovascular-related hospitalizations in patients with ATTR-CM. [Circ Heart Fail 2022;15:e008193]
However, there remains no accepted definition of ATTR‐CM progression or response to therapy, though several measures have been proposed. “Currently available data are insufficient to formulate a standard approach to follow-up and for the surveillance of patients in terms of treatment response and disease progression,” shared Chan.
In general, assessments are conducted based on three aspects: (1) clinical symptoms and functional capacity (clinical assessment-symptom progression, heart failure/arrhythmia episodes; 6-minute walking distance); (2) blood tests for biomarkers (serial monitoring of troponin T, NT-proBNP levels); and (3) transthoracic echocardiography may be used to assess cardiac function (serial monitoring of systolic and diastolic markers, strain imaging). However, the role of imaging modalities in evaluating response to therapy has not yet been established.
“On average, clinical assessments are conducted every 3–4 months but should be adjusted according to the patient’s clinical progression and scenario. Patients with rapid disease progression may require more frequent monitoring, while stable and asymptomatic patients should be assessed at least every 6 months,” she added.
ATTR-CM diagnosis often delayed
ATTR-CM is a devastating condition that has a serious impact on morbidity and mortality. If left untreated, patients often progress to end-stage heart failure, with a poor prognosis. Early diagnosis and treatment are essential for improving prognosis before prolonged amyloid deposition, which eventually leads to symptomatic organ dysfunction. [Orphanet J Rare Dis 2022;17:262]
Regrettably, diagnosis of ATTR-CM is often delayed because of physician- and disease-related reasons, including fragmented knowledge among different specialists and subspecialists, shortage of centres and specialists dedicated to disease management, the perceived rarity of the condition, as well as intrinsic phenotypic and genotypic heterogeneity. [Circ Heart Fail 2019;12:e006075]
“The diagnosis of cardiac amyloidosis relies on a high index of clinical suspicion. However, presenting symptoms and signs can be nonspecific and vague. As such, the condition is underdiagnosed, and diagnosis is often delayed. “To counter this, awareness and understanding of cardiac amyloidosis among physicians and healthcare professionals need to be increased,” said Chan.
Red flags for ATTR-CM
The spectrum of clinical presentations in patients with ATTR-CM obliges all clinicians to be aware of common disease patterns. Table 1 summarizes possible red flags that can be identified from an initial physical examination and assessment of patient history, which may prompt screening of cardiac amyloidosis. Red flags may support a suspicion of ATTR‐CM and lead to subsequent referral to a cardiologist and/or neurologist. [Clin Cardiol 2022;45:898-907]
“Cardiac conditions such as heart failure, abnormal ECG, or abnormal heart rhythm warrant further diagnostic evaluation to ascertain the underlying cause of clinical presentation. Other nonspecific symptoms should be considered in the context of overall clinical risks and signs, as well as family history of hereditary heart conditions,” explained Chan.
“Based on clinical experience, the presenting clinical symptoms and signs of ATTR-CM patients in Asia are similar to those in Europe and the US,” she added.
Diagnostic pathway for ATTR-CM
The diagnostic pathway for ATTR‐CM begins with the suspicion of amyloidosis, followed by initiation of the cardiac workup to assess the patient’s ECG and echocardiography or cardiac magnetic resonance imaging (CMR), if available. If the findings suggest possible cardiac amyloidosis, screening for monoclonal protein followed by scintigraphy or biopsy are recommended. If no monoclonal protein is detected and a diagnosis of AL cardiac amyloidosis is excluded, radionuclide scintigraphy alone without endomyocardial biopsy, can be used to diagnose ATTR-CM. [Clin Cardiol 2022;45:898-907]
The panel recommendations for suspicion and diagnosis of ATTR-CM in Asia are outlined in Table 2.
Treatment response and disease progression
Currently, the only therapy approved for ATTR-CM by the Singapore Health Sciences Authority is tafamidis, a selective transthyretin stabilizer. Randomized clinical trials have shown that tafamidis reduces all-cause mortality and cardiovascular-related hospitalizations in patients with ATTR-CM. [Circ Heart Fail 2022;15:e008193]
However, there remains no accepted definition of ATTR‐CM progression or response to therapy, though several measures have been proposed. “Currently available data are insufficient to formulate a standard approach to follow-up and for the surveillance of patients in terms of treatment response and disease progression,” shared Chan.
In general, assessments are conducted based on three aspects: (1) clinical symptoms and functional capacity (clinical assessment-symptom progression, heart failure/arrhythmia episodes; 6-minute walking distance); (2) blood tests for biomarkers (serial monitoring of troponin T, NT-proBNP levels); and (3) transthoracic echocardiography may be used to assess cardiac function (serial monitoring of systolic and diastolic markers, strain imaging). However, the role of imaging modalities in evaluating response to therapy has not yet been established.
“On average, clinical assessments are conducted every 3–4 months but should be adjusted according to the patient’s clinical progression and scenario. Patients with rapid disease progression may require more frequent monitoring, while stable and asymptomatic patients should be assessed at least every 6 months,” she added.