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Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) benefit from disease-modifying agents such as tafamidis. However, the survival benefit of tafamidis in elderly patients (age ≥80 years) is not reported. This study aimed to assess the survival of patients with ATTR-CM aged 80 years and older who were treated with tafamidis compared with patients aged <80 years. We conducted a retrospective analysis of patients with ATTR-CM who underwent tafamidis treatment, aged 45 to 97 years at the time of diagnosis between January 1, 2008, and May 31, 2021. A total of 484 patients were included, with 208 in the ≥80 years group and 276 in the <80 years group. The cohort was followed up for mortality outcomes, and hazard ratios with 95% confidence intervals were calculated. After a median follow-up of 18.5 months, 72 deaths were recorded in the entire cohort. Kaplan–Meier curves showed no differences in survival probability between the 2 groups at 30 months (p for log-rank test = 0.76). The survival rates for patients aged ≥80 years who underwent treatment at 1, 2, 3, 4, and 5 years were 94.7%, 86.0%, 77.0%, 77.0%, and 38.5%, respectively. The corresponding rates for patients aged <80 years who underwent treatment were 93.2, 84.8, 74.4, 68.2, and 64.6%, respectively. In the multivariable analysis, the hazard ratio (95% confidence interval) of the mortality comparing treatment patients aged ≥80 years with those aged <80 years was 0.81 (0.41 to 1.61). In conclusion, tafamidis treatment is associated with similar reductions in mortality in older and younger patients with ATTR-CM.

Developing predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use two nonhuman primate models to compare the roles of antigen persistence, diversity and innate immunity. We perform longitudinal analyses of HIV Env-specific B-cell receptor responses to SHIV AD8 infection and Env protein vaccination with eight different adjuvants. A subset of the SHIV AD8 -infected animals with higher viral loads and greater Env diversity show increased neutralization associated with increasing somatic hypermutation (SHM) levels over time. The use of adjuvants results in increased ELISA titres but does not affect the mean SHM levels or CDR H3 lengths. Our study shows how the ontogeny of Env-specific B cells can be tracked, and provides insights into the requirements for developing neutralizing antibodies that should facilitate translation to human vaccine studies. HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.

Aims Transthyretin cardiac amyloidosis (ATTR‐CA) is most often associated with heart failure with preserved ejection fraction (HFpEF). However, patients may present with impaired systolic function at the time of diagnosis, which has not been widely investigated. We sought to explore the prevalence of various heart failure (HF) phenotypes and their associated clinical characteristics at the time of ATTR‐CA diagnosis. Methods We performed a single‐centre retrospective cohort study of consecutive patients with ATTR‐CA evaluated between February 2016 and December 2022. Data on patient demographics, comorbidities, imaging and laboratory findings were compared across HF phenotypes (age: 78.1 ± 8.6 years, with 91.1% male). A total of 21.6% (n = 46) presented with heart failure with reduced ejection fraction (HFrEF), 17.8% (n = 38) with heart failure with mildly reduced ejection fraction (HFmrEF) and 60.6% (n = 129) with HFpEF at the time of diagnosis with ATTR‐CA. Those presenting with HFrEF or HFmrEF were more likely to be African American and had significantly worse New York Heart Association (NYHA) functional class, higher N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and higher serum creatinine levels as compared with those with HFpEF. Conclusions Although ATTR‐CA is traditionally thought to be seen primarily among patients with HFpEF, our data suggest that ATTR‐CA has a higher prevalence among patients with HFrEF, which underscores the importance of heightened clinical suspicion regardless of ejection fraction when considering ATTR‐CA. Furthermore, although comorbidities are similar, patients with HFmrEF and HFrEF had a worse symptom burden.

Cardiac amyloidosis (CA), an infiltrative restrictive cardiomyopathy, is a frequently underrecognized etiology of diastolic heart failure (HF). This study aimed to evaluate inpatient outcomes among patients hospitalized with decompensated diastolic HF with and without a secondary diagnosis of amyloidosis, utilizing data from the National Inpatient Sample (2018–2021). Among 2,444,699 patients hospitalized for decompensated diastolic HF, 9205 (0.3%) had a documented secondary diagnosis of amyloidosis. After 1:1 propensity-score matching, 1841 patients in each group were analyzed. Multivariate logistic regression revealed that the presence of amyloidosis was associated with significantly higher odds of in-hospital mortality (4.0% vs. 2.7%), cardiogenic shock (5.4% vs. 2.4%), acute kidney injury (28.3% vs. 22.0%), ventricular tachycardia (12.4% vs. 6.0%), and acute myocardial injury (9.5% vs. 6.0%) (all p < 0.05). Additionally, patients with amyloidosis had a longer mean length of stay (7.1 vs. 5.7 days) and higher mean hospitalization costs ( $85,594 vs. $ 48,484, p < 0.05). Although the overall incidence of acute myocardial injury was elevated, subgroup analysis of ST-elevation and non–ST-elevation myocardial infarction revealed no significant differences. These findings underscore the considerable clinical and economic burden of amyloidosis in patients hospitalized with decompensated diastolic heart failure.

Aims In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1β, in patients with COVID-19, myocardial injury, and heightened inflammation. Methods and results This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo [recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46–2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23–1.64]. At Day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups. Conclusion There was no difference in time to clinical improvement at Day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at Day 28. Graphical Abstract Graphical Abstract