Abstract
Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.
| Original language | English (US) |
|---|---|
| Journal | Amyloid |
| DOIs | |
| State | Accepted/In press - Jan 1 2018 |
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Keywords
- amyloidosis
- cardiomyopathy
- polyneuropathy
- quality of life
- Transthyretin
ASJC Scopus subject areas
- Internal Medicine
Cite this
Hereditary transthyretin amyloidosis : baseline characteristics of patients in the NEURO-TTR trial. / Waddington-Cruz, Marcia; Ackermann, Elizabeth J.; Polydefkis, Michael; Heitner, Stephen B.; Dyck, Peter J.; Barroso, Fabio A.; Wang, Annabel K.; Berk, John L.; Dyck, P. James B.; Monia, Brett P.; Hughes, Steven G.; Tai, Li; Jesse Kwoh, T.; Jung, Shiangtung W.; Coelho, Teresa; Benson, Merrill; Gertz, Morie A.
In: Amyloid, 01.01.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hereditary transthyretin amyloidosis
T2 - baseline characteristics of patients in the NEURO-TTR trial
AU - Waddington-Cruz, Marcia
AU - Ackermann, Elizabeth J.
AU - Polydefkis, Michael
AU - Heitner, Stephen B.
AU - Dyck, Peter J.
AU - Barroso, Fabio A.
AU - Wang, Annabel K.
AU - Berk, John L.
AU - Dyck, P. James B.
AU - Monia, Brett P.
AU - Hughes, Steven G.
AU - Tai, Li
AU - Jesse Kwoh, T.
AU - Jung, Shiangtung W.
AU - Coelho, Teresa
AU - Benson, Merrill
AU - Gertz, Morie A.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.
AB - Background: Hereditary transthyretin (ATTRm) amyloidosis is a rare, progressive and fatal disease with a range of clinical manifestations. Objective: This study comprehensively evaluates disease characteristics in a large, diverse cohort of patients with ATTRm amyloidosis. Methods: Adult patients (N = 172) with Stage 1 or Stage 2 ATTRm amyloidosis who had polyneuropathy were screened and enrolled across 24 investigative sites and 10 countries in the NEURO-TTR trial (www.clinicaltrials.gov, NCT01737398). Medical and disease history, quality of life, laboratory data, and clinical assessments were analyzed. Results: The NEURO-TTR patient population was diverse in age, disease severity, TTR mutation, and organ involvement. Twenty-seven different TTR mutations were present, with Val30Met being the most common (52%). One third of patients reported early onset disease (before age 50) and the average duration of neuropathy symptoms was 5.3 years. Symptoms affected multiple organs and systems, with nearly 70% of patients exhibiting broad involvement of weakness, sensory loss, and autonomic disturbance. Over 60% of patients had cardiomyopathy, with highest prevalence in the United States (72%) and lowest in South America/Australasia (33%). Cardiac biomarker NT-proBNP correlated with left ventricular wall thickness (p<.001). Quality of life, measured by Norfolk QoL-DN and SF-36 patient-reported questionnaires, was significantly impaired and correlated with disease severity. Conclusions: Baseline data from the NEURO-TTR trial demonstrates ATTRm amyloidosis as a systemic disease with deficits in multiple organs and body systems, leading to decreased quality of life. We report concomitant presentation of polyneuropathy and cardiomyopathy in most patients, and early involvement of multiple body systems.
KW - amyloidosis
KW - cardiomyopathy
KW - polyneuropathy
KW - quality of life
KW - Transthyretin
UR - http://www.scopus.com/inward/record.url?scp=85053281731&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053281731&partnerID=8YFLogxK
U2 - 10.1080/13506129.2018.1503593
DO - 10.1080/13506129.2018.1503593
M3 - Article
JO - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
SN - 1350-6129
ER -