Temporal Outcomes of Patients Diagnosed With Transthyretin Cardiac Amyloidosis.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly recognized. Clinical outcomes have evolved over time amid changes in the diagnostic pathway and advances in therapeutics. We sought to evaluate clinical outcomes over time of patients with ATTR-CA with access to disease-modifying therapy. METHODS AND RESULTS: This is a retrospective cohort study of 419 patients diagnosed with ATTR-CA during 2001-2021, comparing clinical characteristics across eras. The primary end point was composite all-cause mortality or orthotopic heart transplantation (OHT). Time-to-event analysis was performed using Cox proportional hazard modeling controlling for differences among cohorts. Patients diagnosed in the more recent years had higher median age (2017-2021, 78 years; 2014-2016, 75 years; 2001-2013, 74 years) and more often had wild-type ATTR (81.9% vs 82.5% vs 56.4%), but less severe phenotypes as evidenced by more individuals with Columbia stage I disease (47.6% vs 35.9% vs 22.4%), owing to lower biomarkers, more patients in New York Heart Association functional classes I and II (68.9% vs 47.6% vs 43.6%), and lower use of loop diuretics (67.0% vs 78.6% vs 89.1%). Over time, patients were treated more frequently with tafamidis (74% vs 37% vs 32%). On multivariable analysis, greater Columbia score (hazard ratio 1.42, 95% confidence interval 1.30-1.54, P < .001) was predictive of death or OHT, whereas tafamidis (hazard ratio 0.31, 95% confidence interval 0.22-0.44, P < .001) was associated with greater survival and freedom from OHT. CONCLUSIONS: Patients recently diagnosed with ATTR-CA have earlier stage disease and substantially lower mortality. Tafamidis is associated with significantly improved survival and freedom from OHT.

Impact of Anemia on Mortality and Morbidity in Transthyretin Amyloid Cardiomyopathy.

Anemia is prevalent in transthyretin amyloid cardiomyopathy (ATTR-CM), but its prognostic significance remains uncertain due to conflicting data mainly in patients not receiving disease-modifying therapy. Additionally, the effect of anemia on morbidity in this population has not been studied. This retrospective study included 270 patients diagnosed with ATTR-CM, receiving disease-modifying treatment (tafamidis), of which 30% (N=80) were anemic (defined as a hemoglobin level <13 g/dL for males and <12 g/dL for females according to the World Health Organization). At baseline, patients with anemia were on average older (mean age 79 vs. 77 years), more likely to be female (21% vs. 12%) and exhibited higher symptom severity based on NYHA class (42% in class III vs. 27%) compared to those without anemia. Additionally, they had a worse Columbia score (mean score 3 vs 5) and Columbia stage (12% in late stage vs. 7.1%) than those without anemia. Kaplan-Meier analysis indicates that anemia was associated with a higher likelihood of mortality, all-cause, and CV hospitalizations (p<0.05). However, in the Cox regression analysis, after adjusting for baseline age, ATTR genotype, and Columbia score, anemia was only associated with a higher risk of all-cause hospitalizations (HR: 1.9 (1.3-2.7), p<0.001) and CV-related hospitalizations (HR: 1.9 (1.2-2.9), p=0.006). In conclusion, this study indicates that anemic patients with ATTR-CM have higher risks of cardiovascular and all-cause hospitalizations compared to non-anemic ATTR-CM patients. Further research is needed to understand how treating anemia may improve outcomes in this high-risk patient population.

Markers of nutritional status and inflammation in transthyretin cardiac amyloidosis: association with outcomes and the clinical phenotype.

Background: Patients with transthyretin (TTR) cardiac amyloidosis demonstrate cardiac cachexia with progression of their cardiomyopathy, which is characterised by malnutrition and a heightened inflammatory state. How best to measure this condition is less well characterised. We investigated differences in survival among patients with ATTR cardiac amyloidosis by nutritional status as defined by modified BMI (mBMI) and by inflammatory state as defined by serum uric acid.Methods and results: This study was a retrospective analysis of patients diagnosed with ATTR cardiac amyloidosis at a single tertiary medical centre. Baseline characteristics were compared by nutritional status as measured by mBMI and by inflammatory state as measured by serum uric acid. Kaplan-Meier survival analyses were used to compare nutritional status and inflammatory status for the composite outcome of death. Cox proportional hazards modelling was used to assess predictors of death in this cohort. Three hundred patients (mean age 75 ± 11) years, 84.3% male) were included. Those with low mBMI (<1185 kg/m2 g/L) had shorter time to death (5.4 vs. 6.8 years, log rank p = .045) and those with elevated serum uric acid (>8.8 mg/dL) had shorter time to death (4.9 vs. 7.7 years, log rank p < .0001). Those with both low mBMI and elevated serum uric acid had the shortest time to death (4.3 years, log rank p = .005). In this cohort, mBMI was not a univariate predictor of death though there was a trend towards significance (HR 0.92, per 100 kg/m2 g/L, 95% CI 0.828-1.016, p = .099). Serum uric acid was a univariate predictor of death (HR 1.27 per 1 mg/dL, 95% CI 1.114-1.455, p < .001). In multivariate Cox analysis, this association remained significant (HR 1.31 per 1 mg/dL increase, 95% CI 1.096-1.560, p = .003) as well as in a separate stepwise model controlling for potential confounders including daily diuretic use, uric acid lowering therapy, and renal dysfunction.Conclusions: Both nutritional status as measured by mBMI and inflammation as measured by serum uric acid are associated with survival in patients with TTR cardiac amyloidosis however only serum uric acid is an independent predictor of death.