Onyedika John Ilonze

Background: Transthyretin amyloid cardiomyopathy (ATTR‐CM) carries high risk for all‐cause mortality (ACM), cardiovascular mortality (CVM), and cardiovascular hospitalization (CVH). NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) and serum TTR (sTTR) are prognostic biomarkers in transthyretin amyloid cardiomyopathy, but their combined value for integrated risk stratification remains unknown. We evaluated the relationship between baseline NT‐proBNP and sTTR and their prognostic value in ATTRIBUTE‐CM (Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy). Methods: ATTRIBUTE‐CM was a phase 3, randomized, double‐blind, placebo‐controlled trial. Among 632 participants randomized to acoramidis or placebo, baseline NT‐proBNP and sTTR concentrations were evaluated post hoc for associations with baseline characteristics, Kansas City Cardiomyopathy Questionnaire overall scores, 6‐minute walk distance, National Amyloidosis Center stage, Geriatric Nutritional Risk Index score, and subsequent time to ACM/first CVH and CVM/first CVH through Month 30. Results: Higher baseline NT‐proBNP and lower sTTR were associated with greater disease severity and were inversely correlated. Using multivariable linear regression, sTTR remained inversely correlated with NT‐proBNP. Using multivariable Cox analyses, baseline NT‐proBNP and sTTR were each independently associated with ACM/first CVH and CVM/first CVH. Higher baseline NT‐proBNP combined with lower sTTR conferred higher risk and shorter time to event. Acoramidis reduced risk of ACM/first CVH and CVM/first CVH regardless of baseline NT‐proBNP/sTTR, National Amyloidosis Center stage, or Geriatric Nutritional Risk Index. Conclusions: Baseline NT‐proBNP and sTTR were additively prognostic for ACM/first CVH and CVM/first CVH in patients with transthyretin amyloid cardiomyopathy. Their joint measurement may be useful for enhanced staging, risk stratification, and prognostication in transthyretin amyloid cardiomyopathy. Acoramidis demonstrated consistent clinical efficacy regardless of baseline NT‐proBNP/sTTR status. Registration: URL: https://clinicaltrials.gov/study/NCT03860935 ; Unique Identifier: NCT03860935. Registered: February 2019.

Candida bloodstream infection (C-BSI) is a rare infection in patients with left ventricular assist devices (LVADs). We aim to describe the characteristics and outcomes of C-BSI. We performed a retrospective search for C-BSI in patients with LVADs at our institution from January 2012 to May 2024. We then performed a literature review using the keywords ‘fungemia ventricular assist device’, ‘candidemia ventricular assist device’, ‘Candida bloodstream infection ventricular assist device,’ or ‘Candida endocarditis ventricular assist device’ from 1990 to 2024. Clinical characteristics and outcomes were extracted. We identified three institutional cases along with 21 additional cases from the literature. The incidence of candidemia was 3.1% (3/97) and 1.8% (16/867), respectively, in the case series and literature review. Mean age was 45.6 years (range 19–73 years), and average body mass index (BMI) was 31.8 kg/m². There was a 100% mortality rate in our cohort and 62.5% in the literature review cohort. Among the surviving patients in the literature review, 66.7% underwent heart transplantation, and 33.3% were discharged on antifungal therapy. 41.2% experienced right heart failure, with four requiring temporary mechanical circulatory support post-operatively. Obesity was present in 75.0% of patients, and 42.1% had an LVAD-related infection. C-BSI developed after an average of 426 days of LVAD support, with 33.3% occurring within 30 days postoperatively. The average duration of C-BSI was 29 days. Candida auris was the most common species. C-BSI is a rare fatal complication in LVAD patients. Obesity, delayed sternal wound closure, and right heart failure may contribute to these poor outcomes.

Background: Racial and ethnic differences in diabetic cardiomyopathy (DbCM) exist, with black and Hispanic participants showing poorer health status. It remains unclear whether these differences affect the natural progression of the disease. We aimed to evaluate disease progression in individuals with DbCM, as well as racial differences in the response to AT-001. Methods: A total of 625 participants with DbCM were randomised to either placebo or AT-001 and followed for 15 months. The primary outcome was change in peak oxygen uptake (peak VO ₂ ) and secondary outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) and Physical Activity Scale for the Elderly scores. Analyses were stratified by race and ethnicity (black, Hispanic, white). Results: Black and Hispanic participants who received placebo experienced greater declines in peak VO ₂ (−0.74 and −1.67 mL/kg/min, respectively) compared with white participants (−0.23 mL/kg/min, p=0.005). AT-001 demonstrated a non-statistically significant trend towards slower declines in peak VO ₂ in black and Hispanic participants (−0.31 and −0.62 mL/kg/min, p=0.29, respectively). Black participants who received placebo had the largest declines in most KCCQ scores. Conclusion: Black and Hispanic participants with DbCM experienced faster disease progression, with black participants showing the most pronounced functional and quality of life declines. The effect of AT-001 on peak VO ₂ changes was not statistically significant with similar effects between racial and ethnic groups ( NCT04083339 ). Trial registration number: NCT04083339 .