United network for organ sharing outcomes after heart transplantation for al compared to ATTR cardiac amyloidosis.
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SUBMITTER: Griffin JM
PROVIDER: S-EPMC7744118 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsThe aims of this study were to assess prescription patterns, dosages, discontinuation rates, and association with prognosis of conventional heart failure medications in patients with transthyretin cardiac amyloidosis (ATTR-CA).Methods and resultsA retrospective analysis of all consecutive patients diagnosed with ATTR-CA at the National Amyloidosis Centre between 2000 and 2022 identified 2371 patients with ATTR-CA. Prescription of heart failure medications was greater among patients with a more severe cardiac phenotype, comprising beta-blockers in 55.4%, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin II receptor blockers (ARBs) in 57.4%, and mineralocorticoid receptor antagonists (MRAs) in 39.0% of cases. During a median follow-up of 27.8 months (interquartile range 10.6-51.3), 21.7% had beta-blockers discontinued, and 32.9% had ACEi/ARBs discontinued. In contrast, only 7.5% had MRAs discontinued. A propensity score-matched analysis demonstrated that treatment with MRAs was independently associated with a reduced risk of mortality in the overall population [hazard ratio (HR) 0.77 (95% confidence interval (CI) 0.66-0.89), P < .001] and in a pre-specified subgroup of patients with a left ventricular ejection fraction (LVEF) >40% [HR 0.75 (95% CI 0.63-0.90), P = .002]; and treatment with low-dose beta-blockers was independently associated with a reduced risk of mortality in a pre-specified subgroup of patients with a LVEF ≤40% [HR 0.61 (95% CI 0.45-0.83), P = .002]. No convincing differences were found for treatment with ACEi/ARBs.ConclusionConventional heart failure medications are currently not widely prescribed in ATTR-CA, and those that received medication had more severe cardiac disease. Beta-blockers and ACEi/ARBs were often discontinued, but low-dose beta-blockers were associated with reduced risk of mortality in patients with a LVEF ≤40%. In contrast, MRAs were rarely discontinued and were associated with reduced risk of mortality in the overall population; but these findings require confirmation in prospective randomized controlled trials.
| S-EPMC10424879 | biostudies-literature
Project description:There are sex differences in mortality while awaiting heart transplantation, and the reason remains unclear. We included all adults in the Scientific Registry of Transplant Recipients placed on the heart transplant active waitlist from 2004 to 2015. The primary end point was all-cause mortality. Multivariable Cox proportional hazards models were performed to evaluate survival by United Network for Organ Sharing (UNOS) status at the time of listing. Random survival forest was used to identify sex interactions for the competing risk of death and transplantation. There were 33 069 patients (25% women) awaiting heart transplantation. This cohort included 7681 UNOS status 1A (26% women), 13 027 UNOS status 1B (25% women), and 12 361 UNOS status 2 (26% women). During a median follow-up of 4.3 months, 1351 women and 4052 men died. After adjusting for >20 risk factors, female sex was associated with a significant risk of death among UNOS status 1A (adjusted hazard ratio, 1.14; 95% confidence interval, 1.01-1.29) and UNOS status 1B (adjusted hazard ratio, 1.17; 95% confidence interval, 1.05-1.30). In contrast, female sex was significantly protective for time to death among UNOS status 2 (adjusted hazard ratio, 0.85; 95% confidence interval, 0.76-0.95). Sex differences in probability of transplantation were present for every UNOS status, and >20 sex interactions were identified for mortality and transplantation. When stratified by initial UNOS status, women had a higher mortality than men as UNOS status 1 and a lower mortality as UNOS status 2. With >20 sex interactions for mortality and transplantation, further evaluation is warranted to form a more equitable allocation system.
| S-EPMC5523830 | biostudies-literature
Project description:BackgroundTransthyretin amyloidosis cardiomyopathy (ATTR-CM) is an underappreciated cause of heart failure that results from misfolded TTR (prealbumin) protein. Diflunisal is an approved non-steroidal anti-inflammatory drug that stabilizes TTR, with limited data available regarding effects on cardiac structure and function.Methods and resultsATTR-CM patients (n=81, 41% treated with 250 mg twice-daily diflunisal by clinical practice) were retrospectively identified with baseline and follow-up (median interval 1 year) serum biomarker and echocardiographic data compared, including global longitudinal strain (GLS). Chi-squared and Wilcoxon tests assessed differences between subjects, divided by treatment group, and univariable and multivariable linear regression was performed. At baseline, patients treated with diflunisal were younger (68 vs 77 years, P = .0001), with lower B-type natriuretic peptide (BNP; 249 vs 545 pg/mL, P = .009) and serum creatinine (1.1 vs 1.2 mg/dL, P = .04), but similar TTR concentration (P = .31), cardiac troponin I (P = .06), and GLS (P = .67). At follow-up, diflunisal untreated versus treated patients showed differences in TTR concentration (19 vs 33 mg/dL, P = .01) and favorable differences in left atrial volume index (+4.6 vs -1.4 mL/m2, P = .002) and cardiac troponin I (+0.03 vs -0.01 ng/mL, P = .01) for the entire cohort. Among the subset with wild-type ATTR (n=53), diflunisal treatment was associated with differences in GLS (+1.2% untreated vs +0.1% treated, P = .03). Changes in wall thickness (P = .2), left ventricular ejection fraction (P = .71), and BNP (P = .42) were similar between groups.ConclusionsIn ATTR-CM, diflunisal treatment resulted in measurable differences in some parameters of cardiac structure and function after only 1 year of administration. Further longer-term analysis is warranted.
| S-EPMC7758872 | biostudies-literature
Project description:BackgroundTransthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy. The clinical course varies among individuals and there are no established measures to assess disease progression.ObjectivesThe goal of this study was to assess the prognostic importance of an increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) as markers of disease progression in a large cohort of patients with ATTR-CA.MethodsWe evaluated landmark survival analysis based on worsening of NT-proBNP and requirement for ODI between time of diagnosis and a 1-year visit, and subsequent mortality in 2,275 patients with ATTR-CA from 7 specialist centers. The variables were developed in the National Amyloidosis Centre (NAC) cohort (n = 1,598) and validated in the external cohort from the remaining centers (n = 677).ResultsBetween baseline and 1-year visits, 551 (34.5%) NAC patients and 204 (30.1%) patients in the external validation cohort experienced NT-proBNP progression (NT-proBNP increase >700 ng/L and >30%), which was associated with mortality (NAC cohort: HR: 1.82; 95% CI: 1.57-2.10; P < 0.001; validation cohort: HR: 1.75; 95% CI: 1.32-2.33; P < 0.001). At 1 year, 451 (28.2%) NAC patients and 301 (44.5%) patients in the external validation cohort experienced ODI, which was associated with mortality (NAC cohort: HR: 1.88; 95% CI: 1.62-2.18; P < 0.001; validation cohort: HR: 2.05; 95% CI: 1.53-2.74; P < 0.001). When compared with patients with a stable NT-proBNP and stable diuretic dose, a higher risk of mortality was observed in those experiencing either NT-proBNP progression or ODI (NAC cohort: HR: 1.93; 95% CI: 1.65-2.27; P < 0.001; validation cohort: HR: 1.94; 95% CI: 1.36-2.77; P < 0.001), and those experiencing both NT-proBNP progression and ODI (NAC cohort: HR: 2.98; 95% CI: 2.42-3.67; P < 0.001; validation cohort: HR: 3.23; 95% CI: 2.17-4.79; P < 0.001).ConclusionsNT-proBNP progression and ODI are frequent and consistently associated with an increased risk of mortality. Combining both variables produces a simple, universally applicable model that detects disease progression in ATTR-CA.
| S-EPMC11004588 | biostudies-literature
Project description:Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal condition that requires early diagnosis, management, and specific treatment. The availability of new disease-modifying therapies has made successful treatment a reality. Transthyretin amyloid cardiomyopathy can be either age-related (wild-type form) or caused by mutations in the TTR gene (genetic, hereditary forms). It is a systemic disease, and while the genetic forms may exhibit a variety of symptoms, a predominant cardiac phenotype is often present. This document aims to provide an overview of ATTR-CM amyloidosis focusing on cardiac involvement, which is the most critical factor for prognosis. It will discuss the available tools for early diagnosis and patient management, given that specific treatments are more effective in the early stages of the disease, and will highlight the importance of a multidisciplinary approach and of specialized amyloidosis centres. To accomplish these goals, the World Heart Federation assembled a panel of 18 expert clinicians specialized in TTR amyloidosis from 13 countries, along with a representative from the Amyloidosis Alliance, a patient advocacy group. This document is based on a review of published literature, expert opinions, registries data, patients' perspectives, treatment options, and ongoing developments, as well as the progress made possible via the existence of centres of excellence. From the patients' perspective, increasing disease awareness is crucial to achieving an early and accurate diagnosis. Patients also seek to receive care at specialized amyloidosis centres and be fully informed about their treatment and prognosis.
| S-EPMC10607607 | biostudies-literature
Project description:ObjectivesWe hypothesized that an increased duration of donor brain death may worsen survival following orthotopic heart transplantation.MethodsThe United Network for Organ Sharing Registry was queried for first-time, adult recipients of heart transplant from 2006 to 2018. Cox proportional hazards with penalized smooth splines was used to stratify patients based on donor brain death interval: shorter (<22 hours), reference (22-42 hours), and longer (>42 hours). Overall survival was estimated using Kaplan-Meier and Cox proportional hazards models.ResultsA total of 22,960 patients met study criteria (9.2% shorter, 55.0% reference, and 35.8% longer). Longer brain death duration recipients were more likely to have a later year of transplant and have a mechanical bridge to transplant, whereas longer duration donors were more likely to be black and die of anoxia compared with shorter duration and reference donors. Compared with reference, neither shorter (hazard ratio, 1.02; 95% confidence interval, 0.94-1.12) nor longer donor brain death interval (hazard ratio, 1.01; 95% CI, 0.94-1.08) was associated with posttransplant survival in either unadjusted or multivariable analyses (both P values >0.6).ConclusionsLonger duration of brain death was not associated with worse survival following heart transplantation. Donors with prolonged interval of brain death should not necessarily be excluded based on brain death period alone.
| S-EPMC6821595 | biostudies-literature
Project description:We evaluated the impact of light chain type, lambda (?) or kappa (?), on disease features and outcomes in patients with immunoglobulin light chain (AL) amyloidosis receiving stem cell transplant at the Mayo Clinic between October 2002 and August 2016. Patients with ? AL amyloidosis had higher rates of renal and neurological involvement (? 69% vs ? 57%, P = .02 and ? 16% vs ? 9%, P = .03, respectively). Patients with ? AL amyloidosis had more hepatic involvement (? 7% vs ? 18%, P = .0003). Complete response rate was 43% for both groups and overall response rates were similar (? 85% vs ? 91%, P = .12). Patients with ? light chain amyloidosis had better progression-free and overall survival (PFS: ? 74 months vs ? 101 months, P = .0064 and OS: ? 121 months vs ? not reached, P = .003). Mayo stage 2004 was more predictive of survival in the ? cohort (median OS of 143 months stage I vs 77 months stage II vs 33 months stage III, P < .0001) than in the ? cohort (median OS not reached for stage I and II and 102 months for stage III, P = .044). Conditioning dose predicted survival in the ? cohort only (median OS 149 months for melphalan 200 mg/m2 vs 50 months for melphalan <200 mg/m2, P < .0001; median OS ? not reached for melphalan 200 mg/m2 or <200 mg/m2, P = .38). On multivariate analysis, light chain type remained an independent predictor of survival. Light chain type predicts organ involvement and survival in patients with AL amyloidosis receiving stem cell transplant.
| S-EPMC5894263 | biostudies-literature
Project description:Development of noninvasive imaging modalities to quantify amyloid burden over time is an unmet clinical need. Technetium pyrophosphate (99mTc-PYP) scintigraphy is a simple and widely available radiotracer useful to differentiate transthyretin from light-chain amyloidosis in patients with advanced cardiac amyloidosis. We examined the utility of serial 99mTc-PYP scanning to quantify amyloid burden over time in TTR cardiac amyloidosis (ATTR-CA).Twenty subjects with ATTR-CA (10 wild type, 10 mutant) underwent serial 99mTc-PYP planar cardiac imaging. Cardiac retention was assessed both semiquantitatively (visual score 0, no uptake to 3, uptake greater than bone) and quantitatively (region of interest drawn over the heart, copied, and mirrored over the contralateral chest) to calculate a heart-to-contralateral (H/CL) ratio. Index scan mean visual score and H/CL were 3.0 ± 0.2 and 1.79 ± 0.2, respectively, and after an average 1.5 ± 0.5 years follow-up, did not differ, 3.0 ± 0.2, P = .33 and 1.76 ± 0.2, P = .44. H/CL change was minimal, 0.03 ± 0.17, did not correlate with time between scans, r = 0.19, P = .43, and was observed despite obvious clinical progression (increase in troponin ? 0.1 ng/mL, BNP ? 400 pg/mL, NYHA class, and/or death).Serial 99mTc-PYP scanning in subjects with advanced ATTR-CA does not show significant changes over an average 1.5 years of follow-up despite obvious clinical progression.
| S-EPMC4826633 | biostudies-other
Project description:Although pathological confirmation is the gold standard for diagnosis of amyloidosis, there is a need for a relevant imaging modality to identify involved organs and evaluate disease extent. Thus, we prospectively investigated imaging findings of Tc-DPD scintigraphy in AL and ATTR amyloidosis.A total of 21 subjects with pathologically confirmed AL or ATTR amyloidosis were included. Pretreatment whole body Tc-DPD planar scanning and regional SPECT/CT were performed in all subjects. For allegedly involved organs, Tc-DPD uptake was visually and semi-quantitatively evaluated on a 4-point scale (grade 0: no uptake, 1: uptake less than spine, 2: uptake similar to spine, and 3: uptake greater than spine).There were 29 organs involved in AL and 12 in ATTR. Significant Tc-DPD uptake was found in 24 organs (sensitivity?=?82.8%) in AL and 9 organs (sensitivity?=?75.0%) in ATTR. Additional SPECT/CT was helpful to ensure abnormal DPD uptake in the involved organs, which was uncertain by attenuation in planar imaging. Degree of Tc-DPD uptake was significantly higher in ATTR compared with AL amyloidosis (P?=?.017). Diffuse soft tissue uptake with photon defects in the liver area was found only in ATTR amyloidosis.This study showed that Tc-DPD scintigraphy might have capacity to differentiate between AL and ATTR subtypes with good sensitivity in various organs involving primary systemic AL and ATTR amyloidosis. Additional SPECT/CT significantly improved the diagnostic efficacy of Tc-DPD scintigraphy.
| S-EPMC7004596 | biostudies-literature
Project description:BackgroundDiagnostic and therapeutic advances have led to much greater awareness of transthyretin cardiac amyloidosis (ATTR-CA). We aimed to characterize changes in the clinical phenotype of patients diagnosed with ATTR-CA over the past 20 years.MethodsThis is a retrospective observational cohort study of all patients referred to the National Amyloidosis Centre (2002-2021) in whom ATTR-CA was a differential diagnosis.ResultsWe identified 2995 patients referred with suspected ATTR-CA, of whom 1967 had a diagnosis of ATTR-CA confirmed. Analysis by 5-year periods revealed an incremental increase in referrals, with higher proportions of patients having been referred after bone scintigraphy and cardiac magnetic resonance imaging (2% versus 34% versus 51% versus 55%, chi-square P<0.001). This was accompanied by a greater number of ATTR-CA diagnoses, predominantly of the wild-type nonhereditary form, which is now the most commonly diagnosed form of ATTR-CA (0% versus 54% versus 67% versus 66%, chi-square P<0.001). Over time, the median duration of associated symptoms before diagnosis fell from 36 months between 2002 and 2006 to 12 months between 2017 and 2021 (Mann-Whitney P<0.001), and a greater proportion of patients had early-stage disease at diagnosis across the 5-year periods (National Amyloidosis Centre stage 1: 34% versus 42% versus 44% versus 53%, chi-square P<0.001). This was associated with more favorable echocardiographic parameters of structure and function, including lesser interventricular septal thickness (18.0±3.8 mm versus 17.2±2.6 mm versus 16.9±2.3 mm versus 16.6±2.4 mm, P=0.01) and higher left ventricular ejection fraction (46.0%±8.9% versus 46.8%±11.0% versus 47.8%±11.0% versus 49.5%±11.1%, P<0.001). Mortality decreased progressively during the study period (2007-2011 versus 2012-2016: hazard ratio, 1.57 [95% CI, 1.31-1.89], P<0.001; and 2012-2016 versus 2017-2021: hazard ratio, 1.89 [95% CI, 1.55-2.30], P<0.001). The proportion of patients enrolled into clinical trials and prescribed disease-modifying therapy increased over the 20-year period, but even when censoring at the trial or medication start date, year of diagnosis remained a significant predictor of mortality (2012-2016 versus 2017-2021: hazard ratio, 1.05 [95% CI, 1.03-1.07], P<0.001).ConclusionsThere has been a substantial increase in ATTR-CA diagnoses, with more patients being referred after local advanced cardiac imaging. Patients are now more often diagnosed at an earlier stage of the disease, with substantially lower mortality. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design.
| S-EPMC9698091 | biostudies-literature