Ruberg Frederick L, Teruya Sergio, Helmke Stephen, Smiley Dia A, Fine Denise, Kurian Damian, Raiszadeh Farbod, Prokaeva Tatiana, Spencer Brian, Wong Sherry, Pandey Shivda, Blaner William S, DeLuca Albert, Johnson Lynne L, Kinkhabwala Mona P, Leb Jay, Mintz Akiva, LaValley Michael P, Einstein Andrew J, Cohn Elizabeth, Gallegos Cesia, Murtagh Gillian, Kelly Jeffery W, Miller Edward J, Maurer Mathew S
Section of Cardiovascular Medicine, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, Massachusetts.
Amyloidosis Center, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts.
JAMA Cardiol. 2025 Sep 10. doi: 10.1001/jamacardio.2025.2948.
Transthyretin cardiac amyloidosis (ATTR-CA) is an underdiagnosed but treatable cause of heart failure (HF) in older individuals that occurs in the context of normal wild-type (ATTRwt-CA) or an abnormal inherited (ATTRv-CA) TTR gene variant. While the most common inherited TTR variant, V142I, occurs in 3% to 4% of self-identified Black Americans and is associated with excess morbidity and mortality, the prevalence of ATTR-CA in this at-risk population is unknown.
To define the prevalence of ATTR-CA and proportions attributable to ATTRwt-CA or ATTRv-CA among older Black and Caribbean Hispanic individuals with HF.
DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter, cross-sectional study was conducted in several major US cities (Boston, Massachusetts; New York, New York; and New Haven, Connecticut) among individuals who self-identified as Black or Caribbean Hispanic older than 60 years with HF. Participants were enrolled between May 2019 and June 2024, and data analysis was conducted from June 2024 to May 2025.
ATTR-CA was determined by radionuclide imaging, with blood testing to exclude light-chain amyloidosis and genotyping to determine TTR gene variant. Echocardiographic, biochemical, physical performance, and quality-of-life data were collected.
Among 646 participants, median (IQR) participant age was 73 (66-80) years, 329 (50.6%) were women, 550 (85.1%) identified as Black, and 186 (28.8%) identified as Caribbean Hispanic. Median (IQR) left ventricular wall thickness was 13 (12-14) mm, and median (IQR) left ventricular ejection fraction was 61% (55%-66%). Overall prevalence of ATTR-CA was 6.66% (95% CI, 4.73%-8.58%), of whom 24 (55.8%) had ATTRwt-CA and 19 (44.2%) had ATTRv-CA owing to V142I. Overall prevalence of V142I allele was 5.6%, and of those, 19 (52.8%) had ATTRv-CA. Prevalence of ATTR-CA was 8.15% (95% CI, 5.15%-11.15%) in men and 5.20% (95% CI, 2.79%-7.61%) in women (P = .13). Prevalence of ATTR-CA was 7.82% (95% CI, 5.57%-10.06%) in Black participants and 2.15% (95% CI, 0.07%-4.24%) in Hispanic participants (P = .004). Among Black participants aged 75 years or younger, ATTR-CA was observed in 3.42% of participants (95% CI, 1.43%-5.40%) compared to 14.04% (95% CI, 9.53%-18.54%) of those older than 75 years (P < .001). Among Black male participants older than 75 years, prevalence of ATTR-CA was 17.17% (95% CI, 9.74%-24.60%).
In this cross-sectional study, ATTR-CA was an important cause of HF in older Black individuals with HF, particularly in men older than 75 years. Approximately half of V142I carriers with HF had ATTR-CA, while 55.8% of all ATTR-CA cases had normal TTR genotype.
ClinicalTrials.gov Identifier: NCT03812172.
转甲状腺素蛋白心脏淀粉样变性（ATTR-CA）是老年人心力衰竭（HF）的一个诊断不足但可治疗的病因，其发生于正常野生型（ATTRwt-CA）或异常遗传性（ATTRv-CA）转甲状腺素蛋白（TTR）基因变异的背景下。虽然最常见的遗传性TTR变异体V142I在3%至4%的自我认定为非裔美国人中出现，并与发病率和死亡率过高相关，但该高危人群中ATTR-CA的患病率尚不清楚。
确定老年黑人和加勒比西班牙裔HF患者中ATTR-CA的患病率以及ATTRwt-CA或ATTRv-CA所占比例。
设计、设置和参与者：这项前瞻性、多中心、横断面研究在美国几个主要城市（马萨诸塞州波士顿；纽约州纽约；康涅狄格州纽黑文）针对自我认定为60岁以上黑人和加勒比西班牙裔的HF患者进行。参与者于2019年5月至2024年6月入组，数据分析于2024年6月至2025年5月进行。
通过放射性核素成像确定ATTR-CA，进行血液检测以排除轻链淀粉样变性，并进行基因分型以确定TTR基因变异。收集超声心动图、生化、身体机能和生活质量数据。
646名参与者中，参与者年龄中位数（IQR）为73（66-80）岁，329名（50.6%）为女性，550名（85.1%）自我认定为黑人，186名（28.8%）自我认定为加勒比西班牙裔。左心室壁厚度中位数（IQR）为13（12-14）mm，左心室射血分数中位数（IQR）为61%（55%-66%）。ATTR-CA的总体患病率为6.66%（95%CI，4.73%-8.58%）其中24名（55.8%）患有ATTRwt-CA，19名（44.2%）因V142I患有ATTRv-CA。V142I等位基因的总体患病率为5.6%，其中19名（52.8%）患有ATTRv-CA。ATTR-CA在男性中的患病率为8.15%（95%CI，5.15%-11.15%），在女性中的患病率为5.20%（95%CI，2.79%-7.61%）（P = 0.13）。ATTR-CA在黑人参与者中的患病率为7.82%（95%CI，5.57%-10.06%），在西班牙裔参与者中的患病率为2.15%（95%CI，0.07%-4.24%）（P = 0.004）。在75岁及以下的黑人参与者中，3.42%的参与者（95%CI,1.43%-5.40%）观察到ATTR-CA，而75岁以上者中这一比例为14.04%（95%CI，9.53%-18.54%）（P < 0.001）。在75岁以上的黑人男性参与者中，ATTR-CA的患病率为17.17%（95%CI，9.74%-24.60%）。
在这项横断面研究中，ATTR-CA是老年黑人HF患者HF的一个重要病因，尤其是在75岁以上的男性中。约一半患有HF的V142I携带者患有ATTR-CA，而所有ATTR-CA病例中有55.8%的TTR基因型正常。
ClinicalTrials.gov标识符：NCT03812172。
