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1. Age- and Sex-Related Differences in Patients With Wild-Type Transthyretin Amyloidosis: Insights From THAOS

Author

Emdin, Michele, Hanna, Mazen, Azevedo, Olga, Lino Cirami, Calogero, Gonzalez Costello, Jose, Slosky, David, Moelgaard, Henning, Nativi Nicolau, Jose, Hummel, Scott, Jeon, Eun-Seok, Fine, Nowell, Murali, Srinivas, Miller, Edward, Shah, Sanjiv, Witteles, Ronald, Waddington-Cruz, Marcia, Lenihan, Daniel, Sekijima, Yoshiki, Van Cleemput, Johan, Correia, Edileide de Barros, Cariou, Eve, Quan, Dianna, Freimer, Miriam, Steidley, David, Hüsing-Kabar, Anna, Plante-Bordeneuve, Violaine, Nienhuis, Hans, Wixner, Jonas, Ralph, Jeffrey, Ventura, Hector, Zivkovic, Sasa, Delgado, Diego, Fernandéz Torrón, Roberto, Gottlieb, Stephen, Cotts, William, Tallaj, Jose, Brunkhorst, Robert, Polydefkis, Michael, Mueller, Christopher, Tschoepe, Carsten, Gonzalez Moreno, Juan, Sarswat, Nitasha, Luo, Jin, Tauras, James, Warner, Alberta, Mora-Ayestaran, Nerea, Dispenzieri, Angela, Kristen, Arnt V., Maurer, Mathew S., Diemberger, Igor, Drachman, Brian M., Grogan, Martha, Gupta, Pritam, Glass, Oliver, Amass, Leslie, and Garcia-Pavia, Pablo

Published
2024
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2. Temporal Trends of Wild-Type Transthyretin Amyloid Cardiomyopathy in the Transthyretin Amyloidosis Outcomes Survey

Author

Barroso, Fabio Adrian, Van Cleemput, Johan, Fine, Nowell, Schmidt, Hartmut, Gess, Burkhard, Moelgaard, Henning, Planté-Bordeneuve, Violaine, Adams, David, Inamo, Jocelyn, Vita, Giuseppe, Cirami, Calogero Lino, Luigetti, Marco, Emdin, Michele, Sekijima, Yoshiki, Yamashita, Taro, Jeon, Eun-Seok, Gonzalez Duarte Briseno, Maria Alejandra, Nienhuis, Hans, Azevedo, Olga, Campistol Plana, Josep Maria, Moreno, Juan Gonzalez, Costello, Jose Gonzalez, Wixner, Jonas, Parman, Yesim, Shah, Sanjiv, Quan, Dianna, Marburger, Tessa, Polydefkis, Michael, Gottlieb, Stephen, Ralph, Jeffrey, Sarswat, Nitasha, Luo, Jin, Murali, Srinivas, Cotts, William, Drachman, Brian, Steidley, David, Hummel, Scott, Slosky, David, Ventura, Hector, Jacoby, Daniel, Hoffman, James, Tauras, James, Zivkovic, Sasa, Tallaj, Jose, Lenihan, Daniel, Mueller, Christopher, Nativi-Nicolau, Jose, Siu, Alfonso, Dispenzieri, Angela, Maurer, Mathew S., Rapezzi, Claudio, Kristen, Arnt V., Garcia-Pavia, Pablo, LoRusso, Samantha, Waddington-Cruz, Márcia, Lairez, Olivier, Witteles, Ronald, Chapman, Doug, Amass, Leslie, and Grogan, Martha

Published
2021
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3. Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS) : 14-year update

Author

Dispenzieri, Angela, Coelho, Teresa, Conceição, Isabel, Waddington-Cruz, Márcia, Wixner, Jonas, Kristen, Arnt V., Rapezzi, Claudio, Planté-Bordeneuve, Violaine, Gonzalez-Moreno, Juan, Maurer, Mathew S., Grogan, Martha, Chapman, Doug, Amass, Leslie, Pavia, Pablo Garcia, Tarnev, Ivaylo, Costello, Jose Gonzalez, Briseno, Maria Alejandra Gonzalez Duarte, Schmidt, Hartmut, Drachman, Brian, Barroso, Fabio Adrian, Yamashita, Taro, Lairez, Olivier, Sekijima, Yoshiki, Vita, Giuseppe, Jeon, Eun-Seok, Hanna, Mazen, Slosky, David, Luigetti, Marco, LoRusso, Samantha, Beamud, Francisco Munoz, Adams, David, Moelgaard, Henning, Press, Rayomand, Cirami, Calogero Lino, Nienhuis, Hans, Plana, Josep Maria Campistol, Inamo, Jocelyn, Jacoby, Daniel, Emdin, Michele, Quan, Dianna, Hummel, Scott, Witteles, Ronald, Dori, Amir, Shah, Sanjiv, Lenihan, Daniel, Azevedo, Olga, Murali, Srinivas, Zivkovic, Sasa, Low, Soon Chai, Nativi-Nicolau, Jose, Fine, Nowell, Tallaj, Jose, Tschoepe, Carsten, Torrón, Roberto Fernandéz, Polydefkis, Michael, Merlini, Giampaolo, Badelita, Sorina, Gottlieb, Stephen, Tauras, James, Correia, Edileide Barros, Ventura, Hector, Gess, Burkhard, Darstein, Felix, Oh, Jeeyoung, Marburger, Tessa, Van Cleemput, Johan, Salutto, Valeria Lujan, Parman, Yesim, Chao, Chi-Chao, Sarswat, Nitasha, Mueller, Christopher, Steidley, David, Ralph, Jeffrey, Warner, Alberta, Cotts, William, Hoffman, James, Rugiero, Marcelo, Misawa, Sonoko, Blanco, Jose Luis Munoz, Davila, Lucia Galan, Sadeh, Menachem, Luo, Jin, Kyriakides, Theodoros, Wang, Annabel, Kaufmann, Horacio, Dispenzieri, Angela, Coelho, Teresa, Conceição, Isabel, Waddington-Cruz, Márcia, Wixner, Jonas, Kristen, Arnt V., Rapezzi, Claudio, Planté-Bordeneuve, Violaine, Gonzalez-Moreno, Juan, Maurer, Mathew S., Grogan, Martha, Chapman, Doug, Amass, Leslie, Pavia, Pablo Garcia, Tarnev, Ivaylo, Costello, Jose Gonzalez, Briseno, Maria Alejandra Gonzalez Duarte, Schmidt, Hartmut, Drachman, Brian, Barroso, Fabio Adrian, Yamashita, Taro, Lairez, Olivier, Sekijima, Yoshiki, Vita, Giuseppe, Jeon, Eun-Seok, Hanna, Mazen, Slosky, David, Luigetti, Marco, LoRusso, Samantha, Beamud, Francisco Munoz, Adams, David, Moelgaard, Henning, Press, Rayomand, Cirami, Calogero Lino, Nienhuis, Hans, Plana, Josep Maria Campistol, Inamo, Jocelyn, Jacoby, Daniel, Emdin, Michele, Quan, Dianna, Hummel, Scott, Witteles, Ronald, Dori, Amir, Shah, Sanjiv, Lenihan, Daniel, Azevedo, Olga, Murali, Srinivas, Zivkovic, Sasa, Low, Soon Chai, Nativi-Nicolau, Jose, Fine, Nowell, Tallaj, Jose, Tschoepe, Carsten, Torrón, Roberto Fernandéz, Polydefkis, Michael, Merlini, Giampaolo, Badelita, Sorina, Gottlieb, Stephen, Tauras, James, Correia, Edileide Barros, Ventura, Hector, Gess, Burkhard, Darstein, Felix, Oh, Jeeyoung, Marburger, Tessa, Van Cleemput, Johan, Salutto, Valeria Lujan, Parman, Yesim, Chao, Chi-Chao, Sarswat, Nitasha, Mueller, Christopher, Steidley, David, Ralph, Jeffrey, Warner, Alberta, Cotts, William, Hoffman, James, Rugiero, Marcelo, Misawa, Sonoko, Blanco, Jose Luis Munoz, Davila, Lucia Galan, Sadeh, Menachem, Luo, Jin, Kyriakides, Theodoros, Wang, Annabel, and Kaufmann, Horacio

Abstract

Background: Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods: Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results: This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions: This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745.

Published
2022
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4. Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Author

Dispenzieri, Angela, Coelho, Teresa, Conceição, Isabel, Waddington-Cruz, Márcia, Wixner, Jonas, Kristen, Arnt V., Rapezzi, Claudio, Planté-Bordeneuve, Violaine, Gonzalez-Moreno, Juan, Maurer, Mathew S., Grogan, Martha, Chapman, Doug, Amass, Leslie, Pavia, Pablo Garcia, Tarnev, Ivaylo, Costello, Jose Gonzalez, Briseno, Maria Alejandra Gonzalez Duarte, Schmidt, Hartmut, Drachman, Brian, Barroso, Fabio Adrian, Yamashita, Taro, Lairez, Olivier, Sekijima, Yoshiki, Vita, Giuseppe, Jeon, Eun-Seok, Hanna, Mazen, Slosky, David, Luigetti, Marco, LoRusso, Samantha, Beamud, Francisco Munoz, Adams, David, Moelgaard, Henning, Press, Rayomand, Cirami, Calogero Lino, Nienhuis, Hans, Plana, Josep Maria Campistol, Inamo, Jocelyn, Jacoby, Daniel, Emdin, Michele, Quan, Dianna, Hummel, Scott, Witteles, Ronald, Dori, Amir, Shah, Sanjiv, Lenihan, Daniel, Azevedo, Olga, Murali, Srinivas, Zivkovic, Sasa, Low, Soon Chai, Nativi-Nicolau, Jose, Fine, Nowell, Tallaj, Jose, Tschoepe, Carsten, Torrón, Roberto Fernandéz, Polydefkis, Michael, Merlini, Giampaolo, Badelita, Sorina, Gottlieb, Stephen, Tauras, James, Correia, Edileide Barros, Ventura, Hector, Gess, Burkhard, Darstein, Felix, Oh, Jeeyoung, Marburger, Tessa, Van Cleemput, Johan, Salutto, Valeria Lujan, Parman, Yesim, Chao, Chi-Chao, Sarswat, Nitasha, Mueller, Christopher, Steidley, David, Ralph, Jeffrey, Warner, Alberta, Cotts, William, Hoffman, James, Rugiero, Marcelo, Misawa, Sonoko, Blanco, Jose Luis Munoz, Davila, Lucia Galan, Sadeh, Menachem, Luo, Jin, Kyriakides, Theodoros, Wang, Annabel, and Kaufmann, Horacio

Subjects
Male, Amyloid Neuropathies, Familial, Registry, Neurologi, Cardiomyopathy, General Medicine, Amyloidosis, Genetic Profile, Amyloid Neuropathies, Transthyretin, Phenotype, Familial, Neurology, Surveys and Questionnaires, Polyneuropathy, Humans, Prealbumin, Pharmacology (medical), Female, Genetics (clinical)
Abstract

Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745.

Published
2022

5. Temporal Trends of Wild-Type Transthyretin Amyloid Cardiomyopathy in the Transthyretin Amyloidosis Outcomes Survey

Author

Nativi-Nicolau, Jose, primary, Siu, Alfonso, additional, Dispenzieri, Angela, additional, Maurer, Mathew S., additional, Rapezzi, Claudio, additional, Kristen, Arnt V., additional, Garcia-Pavia, Pablo, additional, LoRusso, Samantha, additional, Waddington-Cruz, Márcia, additional, Lairez, Olivier, additional, Witteles, Ronald, additional, Chapman, Doug, additional, Amass, Leslie, additional, Grogan, Martha, additional, Barroso, Fabio Adrian, additional, Van Cleemput, Johan, additional, Fine, Nowell, additional, Schmidt, Hartmut, additional, Gess, Burkhard, additional, Moelgaard, Henning, additional, Planté-Bordeneuve, Violaine, additional, Adams, David, additional, Inamo, Jocelyn, additional, Vita, Giuseppe, additional, Cirami, Calogero Lino, additional, Luigetti, Marco, additional, Emdin, Michele, additional, Sekijima, Yoshiki, additional, Yamashita, Taro, additional, Jeon, Eun-Seok, additional, Gonzalez Duarte Briseno, Maria Alejandra, additional, Nienhuis, Hans, additional, Azevedo, Olga, additional, Campistol Plana, Josep Maria, additional, Moreno, Juan Gonzalez, additional, Costello, Jose Gonzalez, additional, Wixner, Jonas, additional, Parman, Yesim, additional, Shah, Sanjiv, additional, Quan, Dianna, additional, Marburger, Tessa, additional, Polydefkis, Michael, additional, Gottlieb, Stephen, additional, Ralph, Jeffrey, additional, Sarswat, Nitasha, additional, Luo, Jin, additional, Murali, Srinivas, additional, Cotts, William, additional, Drachman, Brian, additional, Steidley, David, additional, Hummel, Scott, additional, Slosky, David, additional, Ventura, Hector, additional, Jacoby, Daniel, additional, Hoffman, James, additional, Tauras, James, additional, Zivkovic, Sasa, additional, Tallaj, Jose, additional, Lenihan, Daniel, additional, and Mueller, Christopher, additional

Published
2021
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6. Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - Report from the Transthyretin Amyloidosis Outcome Survey (THAOS)

Author

Kristen, Arnt V., Maurer, Mathew S., Rapezzi, Claudio, Mundayat, Rajiv, Suhr, Ole B., Damy, Thibaud, Barroso, Fabio Adrian, Rugiero, Marcelo F, Van Cleemput, Johan J., Tournev, Ivailo, Cruz, Marcia Waddington, Fine, Nowell M., Kristen, Arnt Volko, Schmidt, Hartmut H. J., Zimmermann, Tim, Gess, Burkhard, Moelgaard, Henning, Plana, Josep Maria Campistol, Reines, Juan Buades, Costello, Jose Gonzalez, Pavia, Pablo Garcia, Blanco, Jose Luis Munoz, Plante Bordeneuve, Violaine, Adams, David, Inamo, Jocelyn, Vita, Giuseppe, Merlini, Giampaolo, Bergesio, Franco, Sekijima, Yoshiki, Ando, Yukio, Misawa, Sonoko, Lee, Ga Yeon, Jeeyoung, Oh, Briseno, Maria Alejandra Gonzalez Duarte, Hazenberg, Bouke P. C., Coelho, Teresa, Conceicao, Isabel M., Maurer, Mathew Shane, Shah, Sanjiv Jayendra, Quan, Dianna, Judge, Daniel Philip, Gottlieb, Stephen Scott, Sarswat, Nitasha, Murali, Srinivas C., Iyadurai, Stanley, Cotts, William Gerritt, Drachman, Brian M., Dispenzieri, Angela, Steidley, David Eric, Hummel, Scott L., Lenihan, Daniel J., Ventura, Hector Osvaldo, Jacoby, Daniel L., Hoffman, James E., Kristen, Arnt V., Maurer, Mathew S., Rapezzi, Claudio, Mundayat, Rajiv, Suhr, Ole B., Damy, Thibaud, Barroso, Fabio Adrian, Rugiero, Marcelo F, Van Cleemput, Johan J., Tournev, Ivailo, Cruz, Marcia Waddington, Fine, Nowell M., Kristen, Arnt Volko, Schmidt, Hartmut H.J., Zimmermann, Tim, Gess, Burkhard, Moelgaard, Henning, Plana, Josep Maria Campistol, Reines, Juan Buade, Costello, Jose Gonzalez, Pavia, Pablo Garcia, Blanco, Jose Luis Munoz, Plante-Bordeneuve, Violaine, Adams, David, Inamo, Jocelyn, Vita, Giuseppe, Merlini, Giampaolo, Bergesio, Franco, Sekijima, Yoshiki, Ando, Yukio, Misawa, Sonoko, Lee, Ga Yeon, Oh, Jeeyoung, Briseno, Maria Alejandra Gonzalez Duarte, Hazenberg, Bouke P.C., Coelho, Teresa, Conceicao, Isabel M., Maurer, Mathew Shane, Shah, Sanjiv Jayendra, Quan, Dianna, Judge, Daniel Philip, Gottlieb, Stephen Scott, Sarswat, Nitasha, Murali, Srinivas C., Iyadurai, Stanley, Cotts, William Gerritt, Drachman, Brian M., Dispenzieri, Angela, Steidley, David Eric, Hummel, Scott L., Lenihan, Daniel J., Ventura, Hector Osvaldo, Jacoby, Daniel L., Hoffman, James E., and Translational Immunology Groningen (TRIGR)

Subjects
Genetics and Molecular Biology (all), Pathology, Physiology, medicine.medical_treatment, Peptide Hormones, lcsh:Medicine, Medicine (all), Biochemistry, Agricultural and Biological Sciences (all), 030204 cardiovascular system & hematology, Liver transplantation, Pathology and Laboratory Medicine, Body Mass Index, 0302 clinical medicine, Genotype-phenotype distinction, Surveys and Questionnaires, Genotype, Natriuretic Peptide, Brain, Natriuretic peptide, Medicine and Health Sciences, Atrial natriuretic peptides, Cardiac and Cardiovascular Systems, lcsh:Science, Multidisciplinary, Kardiologi, biology, Amyloidosis, Biochemical markers, Troponin, Phenotype, Physiological Parameters, cardiovascular system, Anatomy, hormones, hormone substitutes, and hormone antagonists, Research Article, medicine.medical_specialty, medicine.drug_class, Cardiology, Surgical and Invasive Medical Procedures, macromolecular substances, NO, 03 medical and health sciences, Digestive System Procedures, Signs and Symptoms, Troponin T, Diagnostic Medicine, Natriuretic Peptide, medicine, Humans, cardiovascular diseases, Heart Failure, Amyloid Neuropathies, Familial, Transplantation, Biochemistry, Genetics and Molecular Biology (all), business.industry, lcsh:R, Troponin I, Body Weight, Biology and Life Sciences, Proteins, Renal System, Organ Transplantation, medicine.disease, Hormones, Liver Transplantation, Transthyretin, Cytoskeletal Proteins, Heart failure, biology.protein, lcsh:Q, business, 030217 neurology & neurosurgery, Biomarkers
Abstract

AIM:Cardiac troponins and natriuretic peptides are established for risk stratification in light-chain amyloidosis. Data on cardiac biomarkers in transthyretin amyloidosis (ATTR) are lacking. METHODS AND RESULTS:Patients (n = 1617) with any of the following cardiac biomarkers, BNP (n = 1079), NT-proBNP (n = 550), troponin T (n = 274), and troponin I (n = 108), available at baseline in the Transthyretin Amyloidosis Outcomes Survey (THAOS) were analyzed for differences between genotypes and phenotypes and their association with survival. Median level of BNP was 68.0 pg/mL (IQR 30.5-194.9), NT-proBNP 337.9 pg/mL (IQR 73.0-2584.0), troponin T 0.03 μg/L (IQR 0.01-0.05), and troponin I 0.08 μg/L (IQR 0.04-0.13). NT-proBNP and BNP were higher in wild-type than mutant-type ATTR, troponin T and I did not differ, respectively. Non-Val30Met patients had higher BNP, NT-proBNP and troponin T levels than Val30Met patients, but not troponin I. Late-onset Val30Met was associated with higher levels of troponin I and troponin T compared with early-onset. 115 patients died during a median follow-up of 1.2 years. Mortality increased with increasing quartiles (BNP/NT-proBNP Q1 = 1.7%, Q2 = 5.2%, Q3 = 21.7%, Q4 = 71.3%; troponin T/I Q1 = 6.5%, Q2 = 14.5%, Q3 = 33.9%, Q4 = 45.2%). Three-year overall-survival estimates for BNP/NT-proBNP and troponin T/I quartiles differed significantly (p

Published
2017

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