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JAMA Cardiology Jan 2024Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo. However, its effect on cardiac... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Tafamidis has been shown to improve survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) compared with placebo. However, its effect on cardiac function has not been fully characterized.
OBJECTIVE
To examine the effect of tafamidis on cardiac function in patients with ATTR-CM.
DESIGN, SETTING, AND PARTICIPANTS
This was an exploratory, post hoc analysis of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), a multicenter, international, double-blind, placebo-controlled phase 3 randomized clinical trial conducted from December 2013 to February 2018. The ATTR-ACT included 48 sites in 13 counties and enrolled patients aged 18 to 90 years with ATTR-CM. Data were analyzed from July 2018 to September 2023.
INTERVENTION
Patients were randomized to tafamidis meglumine, 80 mg or 20 mg, or placebo for 30 months.
MAIN OUTCOMES AND MEASURES
Patients were categorized based on left ventricular (LV) ejection fraction at enrollment as having heart failure with preserved ejection fraction (≥50%), mildly reduced ejection fraction (41% to 49%), or reduced ejection fraction (≤40%). Changes from baseline to month 30 in LV ejection fraction, LV stroke volume, LV global longitudinal strain, and the ratio of early mitral inflow velocity to septal and lateral early diastolic mitral annular velocity (E/e') were compared in patients receiving tafamidis, 80 mg, vs placebo.
RESULTS
A total of 441 patients were randomized in ATTR-ACT, and 436 patients had available echocardiographic data. Of 436 included patients, 393 (90.1%) were male, and the mean (SD) age was 74 (7) years. A total of 220 (50.5%), 119 (27.3%), and 97 (22.2%) had heart failure with preserved, mildly reduced, and reduced LV ejection fraction, respectively. Over 30 months, there was less pronounced worsening in 4 of the echocardiographic measures in patients receiving tafamidis, 80 mg (n = 176), vs placebo (n = 177) (least squares mean difference: LV stroke volume, 7.02 mL; 95% CI, 2.55-11.49; P = .002; LV global longitudinal strain, -1.02%; 95% CI, -1.73 to -0.31; P = .005; septal E/e', -3.11; 95% CI, -5.50 to -0.72; P = .01; lateral E/e', -2.35; 95% CI, -4.01 to -0.69; P = .006).
CONCLUSIONS AND RELEVANCE
Compared with placebo, tafamidis, 80 mg, attenuated the decline of LV systolic and diastolic function over 30 months in patients with ATTR-CM. Approximately half of patients had mildly reduced or reduced LV ejection fraction at enrollment, suggesting that ATTR-CM should be considered as a possible diagnosis in patients with heart failure regardless of underlying LV ejection fraction.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT01994889.
Topics: Female; Humans; Male; Amyloidosis; Cardiomyopathies; Heart Failure; Prealbumin; Ventricular Dysfunction, Left; Adolescent; Young Adult; Adult; Middle Aged; Aged; Aged, 80 and over
PubMed: 37966817
DOI: 10.1001/jamacardio.2023.4147 -
JACC. Heart Failure Jan 2024Tafamidis was approved to treat patients with transthyretin amyloid cardiomyopathy (ATTR-CM) on the basis of findings from the phase 3 Tafamidis in Transthyretin...
BACKGROUND
Tafamidis was approved to treat patients with transthyretin amyloid cardiomyopathy (ATTR-CM) on the basis of findings from the phase 3 Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT).
OBJECTIVES
This study was a post hoc analysis exploring tafamidis efficacy in octogenarian patients.
METHODS
Analysis of patients aged <80 and ≥80 years in ATTR-ACT and its ongoing open-label long-term extension (LTE) study, where all patients receive tafamidis.
RESULTS
After 30 months in ATTR-ACT, least squares (LS) mean change from baseline in 6-minute walk test (6MWT) distance, N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration, and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score were smaller (all P < 0.05) in patients aged ≥80 years treated with tafamidis (n = 51) vs placebo (n = 37). At the LTE study interim analysis, patients aged ≥80 years treated continuously with tafamidis had a smaller decline in KCCQ-OS score (P < 0.05) and trended toward longer median survival (45 vs 27 months; all-cause mortality HR: 0.6828 [95% CI: 0.4048-1.1517]; P = 0.1526) than those initially treated with placebo in ATTR-ACT. Similar efficacy was observed in patients aged <80 years in ATTR-ACT, including smaller LS mean change from baseline in 6MWT distance, NT-proBNP concentration, and KCCQ-OS score, and lower rate of cardiovascular-related hospitalizations with tafamidis (n = 125) vs placebo (n = 140). In the LTE study, patients aged <80 years treated continuously with tafamidis had a longer median survival (80 vs 41 months; HR = 0.4513 [95% CI: 0.3176-0.6413]; P < 0.0001) and a smaller decline in KCCQ-OS score than those initially treated with placebo.
CONCLUSIONS
The findings demonstrate tafamidis efficacy for patients with ATTR-CM both in those aged <80 and those aged ≥80 years. (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial [ATTR-ACT]; NCT01994889/Long-term Safety of Tafamidis in Subjects With Transthyretin Cardiomyopathy; NCT02791230).
Topics: Aged; Aged, 80 and over; Humans; Amyloid Neuropathies, Familial; Cardiomyopathies; Heart Failure; Octogenarians; Prealbumin; Clinical Trials, Phase III as Topic
PubMed: 37943223
DOI: 10.1016/j.jchf.2023.08.032 -
Current and Evolving Multimodality Cardiac Imaging in Managing Transthyretin Amyloid Cardiomyopathy.JACC. Cardiovascular Imaging Feb 2024Amyloid transthyretin (ATTR) amyloidosis is a protein-misfolding disease characterized by fibril accumulation in the extracellular space that can result in local tissue... (Review)
Review
Amyloid transthyretin (ATTR) amyloidosis is a protein-misfolding disease characterized by fibril accumulation in the extracellular space that can result in local tissue disruption and organ dysfunction. Cardiac involvement drives morbidity and mortality, and the heart is the major organ affected by ATTR amyloidosis. Multimodality cardiac imaging (ie, echocardiography, scintigraphy, and cardiac magnetic resonance) allows accurate diagnosis of ATTR cardiomyopathy (ATTR-CM), and this is of particular importance because ATTR-targeting therapies have become available and probably exert their greatest benefit at earlier disease stages. Apart from establishing the diagnosis, multimodality cardiac imaging may help to better understand pathogenesis, predict prognosis, and monitor treatment response. The aim of this review is to give an update on contemporary and evolving cardiac imaging methods and their role in diagnosing and managing ATTR-CM. Further, an outlook is presented on how artificial intelligence in cardiac imaging may improve future clinical decision making and patient management in the setting of ATTR-CM.
Topics: Humans; Prealbumin; Artificial Intelligence; Predictive Value of Tests; Amyloid Neuropathies, Familial; Cardiomyopathies
PubMed: 38099914
DOI: 10.1016/j.jcmg.2023.10.010 -
Clinical Nutrition (Edinburgh, Scotland) Oct 2023The potential effects of resistance training on sarcopenia in patients with intestinal failure (IF) are not fully elucidated. This study aimed to explore the efficacy of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The potential effects of resistance training on sarcopenia in patients with intestinal failure (IF) are not fully elucidated. This study aimed to explore the efficacy of a resistance training program on appendicular skeletal muscle index (ASMI), physical performance, body composition, biochemical parameters, and health-related quality of life (HRQOL) in patients with IF exhibiting sarcopenia.
METHODS
A single-center randomized controlled trial was conducted in a Chinese tertiary teaching hospital. Patients with IF exhibiting sarcopenia were randomly assigned to the exercise group or control group. Participants in the exercise group incorporated four sets of resistance training involving the limbs and abdominal and lower back muscles, six times weekly for 4 weeks. The control group received no specific intervention. The primary outcome was the between-group difference in ASMI 4 weeks after intervention. Secondary outcomes included handgrip strength, 6-m gait speed, body composition, biochemical parameters, and HRQOL.
RESULTS
A total of 60 participants (control group 30, age 51.2 ± 12.9 years, women 43.3%; exercise group 30, age 53.9 ± 14.5 years, women 56.7%) completed the 4-week intervention trial. For the primary outcome, significant intervention effects were found in ASMI between the exercise group and the control group (mean difference 0.72, 95% CI, 0.56-0.89, P < 0.001). There were notable differences in handgrip strength (mean difference 2.7, 95% CI, 1.7-3.6, P < 0.001), 6-m gait speed (mean difference 0.08, 95% CI, 0.01-0.35, P = 0.034), body composition (including total cell mass, bone mineral content, skeletal muscle mass, lean mass, visceral fat area, total body water, intracellular water, extracellular water, and segmental water-legs), and biochemical parameters (including IGF-1, prealbumin, and hemoglobin) between the two groups (P < 0.05). No significant intervention benefits were observed for other secondary outcomes, including biochemical parameters (including albumin, total bilirubin, etc.) and HRQOL (P > 0.05).
CONCLUSIONS
In this randomized clinical trial, we observed that 4 weeks of resistance training was associated with improved ASMI, physical performance, biochemical parameters (including IGF-1, prealbumin, and hemoglobin), and body composition in IF patients with sarcopenia. Resistance training can be recommended as a simple and effective method to improve sarcopenia in patients with IF.
CLINICAL TRIAL REGISTRATION
www.chictr.org.cn, identifier: ChiCTR2100051727.
Topics: Humans; Female; Adult; Middle Aged; Aged; Sarcopenia; Muscle Strength; Insulin-Like Growth Factor I; Prealbumin; Hand Strength; Resistance Training; Quality of Life; Intestinal Failure; Muscle, Skeletal
PubMed: 37625319
DOI: 10.1016/j.clnu.2023.07.013 -
Global Heart 2023Transthyretin cardiac amyloidosis (ATTR-CA) has been traditionally considered a rare and inexorably fatal condition. ATTR-CA now is an increasingly recognised cause of...
Transthyretin cardiac amyloidosis (ATTR-CA) has been traditionally considered a rare and inexorably fatal condition. ATTR-CA now is an increasingly recognised cause of heart failure and mortality worldwide with effective pharmacological treatments. Advances in non-invasive diagnosis, coupled with the development of effective treatments, have transformed the diagnosis of ATTR-CA, which is now possible without recourse to endomyocardial biopsy in around 70% of cases. Many patients are now diagnosed at an earlier stage. Echocardiography and cardiac magnetic resonance have enabled identification of patients with possible ATTR-CA and more accurate prognostic stratification. Therapies able to slow or halt ATTR-CA progression and increase survival are now available and there is also evidence that patients may benefit from specific conventional heart failure medications. A wide horizon of possibilities is unfolding and awaits discovery.
Topics: Humans; Prealbumin; Amyloidosis; Heart Failure; Prognosis; Cardiomyopathies
PubMed: 38028963
DOI: 10.5334/gh.1275 -
JAMA Jun 2024Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart... (Observational Study)
Observational Study
IMPORTANCE
Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments.
OBJECTIVES
To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population.
DESIGN, SETTING, AND PARTICIPANTS
A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024.
EXPOSURE
V142I carrier status (n = 754, 3.2%).
MAIN OUTCOMES AND MEASURES
Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data.
RESULTS
Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant.
CONCLUSIONS AND RELEVANCE
Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Amyloidosis; Black or African American; Cardiomyopathies; Disease Progression; Heart Failure; Heterozygote; Hospitalization; Prealbumin; Stroke Volume; United States; Cost of Illness
PubMed: 38734952
DOI: 10.1001/jama.2024.4467 -
Journal of the American Heart... Aug 2023
Topics: Humans; Aged; Prealbumin; Penetrance; Amyloidosis; Heart Failure; Health Disparate Minority and Vulnerable Populations
PubMed: 37486081
DOI: 10.1161/JAHA.123.030802 -
Journal of the American College of... Mar 2024Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most... (Review)
Review
Cardiac amyloidosis is increasingly recognized as a treatable form of heart failure. Highly effective specific therapies have recently become available for the 2 most frequent forms of cardiac amyloidosis: immunoglobulin light chain amyloidosis and transthyretin (ATTR) amyloidosis. Nevertheless, initiation of specific therapies requires recognition of cardiac amyloidosis and appropriate characterization of the amyloid type. Although noninvasive diagnosis is possible for ATTR cardiac amyloidosis, histological demonstration and typing of amyloid deposits is still required for a substantial number of patients with ATTR and in all patients with light chain amyloidosis and other rarer forms of cardiac amyloidosis. Amyloid histological typing can be performed using different techniques: mass spectrometry, immunohistochemistry, and immunoelectron microscopy. This review describes which patients require histological confirmation of cardiac amyloidosis along with when and how to type amyloid deposits in histologic specimens. Furthermore, it covers the characteristics and limitations of the different typing methods that are available in clinical practice.
Topics: Humans; Plaque, Amyloid; Amyloidosis; Amyloid; Heart Failure; Immunohistochemistry; Amyloidogenic Proteins; Prealbumin; Amyloid Neuropathies, Familial; Cardiomyopathies
PubMed: 38479957
DOI: 10.1016/j.jacc.2024.01.010 -
Journal of the American Heart... Aug 2023Background The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR-CM) increase with age, and they often coexist. The objective was to... (Clinical Trial)
Clinical Trial
Background The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR-CM) increase with age, and they often coexist. The objective was to determine the prevalence of ATTR-CM in patients with severe aortic stenosis and evaluate differences in presentations and outcomes of patients with concomitant ATTR-CM undergoing transcatheter aortic valve implantation. Methods and Results Prospective screening for ATTR-CM with Technetium-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy was performed in 315 patients referred with severe aortic stenosis between August 2019 and August 2021. Myocardial Technetium-3,3-diphosphono-1,2-propanodicarboxylic acid tracer uptake was detected in 34 patients (10.8%), leading to a diagnosis of ATTR-CM in 30 patients (Perugini ≥2: 9.5%). Age (85.7±4.9 versus 82.8±4.5; =0.001), male sex (82.4% versus 57.7%; =0.005), and prior carpal tunnel surgery (17.6% versus 4.3%; =0.007) were associated with coexisting ATTR-CM, as were ECG (discordant QRS voltage to left ventricular wall thickness [42% versus 12%; <0.001]), echocardiographic (left ventricular ejection fraction 48.8±12.8 versus 58.4±10.8; <0.001; left ventricular mass index, 144.4±45.8 versus 117.2±34.4g/m; <0.001), and hemodynamic parameters (mean aortic valve gradient, 23.4±12.6 versus 35.5±16.6; <0.001; mean pulmonary artery pressure, 29.5±9.7 versus 25.8±9.5; =0.037). Periprocedural (cardiovascular death: hazard ratio [HR], 0.71 [95% CI, 0.04-12.53]; stroke: HR, 0.46 [95% CI, 0.03-7.77]; pacemaker implantation: HR, 1.54 [95% CI, 0.69-3.43]) and 1-year clinical outcomes (cardiovascular death: HR, 1.04 [95% CI, 0.37-2.96]; stroke: HR, 0.34 [95% CI, 0.02-5.63]; pacemaker implantation: HR, 1.50 [95% CI, 0.67-3.34]) were similar between groups. Conclusions Coexisting ATTR-CM was observed in every 10th elderly patient with severe aortic stenosis referred for therapy. While patients with coexisting pathologies differ in clinical presentation and echocardiographic and hemodynamic parameters, peri-interventional risk and early clinical outcomes were comparable up to 1 year after transcatheter aortic valve implantation. REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT04061213.
Topics: Aged; Humans; Male; Amyloidosis; Aortic Valve; Aortic Valve Stenosis; Cardiomyopathies; Prealbumin; Prospective Studies; Stroke; Stroke Volume; Technetium; Tomography, X-Ray Computed; Transcatheter Aortic Valve Replacement; Treatment Outcome; Ventricular Function, Left
PubMed: 37581394
DOI: 10.1161/JAHA.123.030271 -
Dysphagia Dec 2023To observe the clinical effects of transcranial direct current stimulation (tDCS) combined with conventional swallowing rehabilitation training on post-stroke dysphagia... (Randomized Controlled Trial)
Randomized Controlled Trial
To observe the clinical effects of transcranial direct current stimulation (tDCS) combined with conventional swallowing rehabilitation training on post-stroke dysphagia and explore its long-term efficacy. A total of 40 patients with dysphagia after the first stroke were randomly divided into a treatment group (n = 20) and a conventional group (n = 20). The treatment group received tDCS combined with conventional swallowing rehabilitation training, while the conventional group only received conventional swallowing rehabilitation training. The Standardized Swallowing Assessment (SSA) Scale and the Penetration-Aspiration Scale (PAS) were used to assess dysphagia before and after treatment, at the end of 10 treatments, and at the 3-month follow-up. The changes in infection indicators [the white blood cell (WBC), C-reactive protein (CRP) and procalcitonin (PCT)], the oxygenation indicator [arterial partial pressure of oxygen (PaO)] and nutrition-related indicators [hemoglobin (Hb) and serum prealbumin (PAB)] were compared before and after treatment. The SSA and PAS scores were lower in both groups after treatment than before treatment, and the difference was statistically significant (P < 0.01). The SSA and PAS scores of the treatment group were lower than those of the conventional group before and after treatment and during follow-up, and the difference was statistically significant (P < 0.05, P < 0.01). A within-group comparison showed that WBC, CRP and PCT after treatment were lower than those before treatment, and the difference was statistically significant (P < 0.05). The PaO, Hb and serum PAB were higher after treatment than before treatment, with a statistically significant difference (P < 0.05). The WBC, CRP and PCT of the tDCS group were lower than those of the conventional group, and PaO, Hb and serum PAB were higher in the treatment group than in the conventional group, with a statistically significant difference (P < 0.01). The tDCS combined with conventional swallowing rehabilitation training can improve dysphagia with a better effect than conventional swallowing rehabilitation training and has a certain long-term efficacy. In addition, tDCS combined with conventional swallowing rehabilitation training can improve nutrition and oxygenation and reduce infection levels.
Topics: Humans; Deglutition Disorders; Transcranial Direct Current Stimulation; Deglutition; Treatment Outcome; Stroke; Stroke Rehabilitation
PubMed: 37142734
DOI: 10.1007/s00455-023-10581-2