Conventional heart failure medication in immunoglobulin light-chain cardiac amyloidosis
C Nitsche, L L List, C K Kronberger, A C Cunha, S K Kroll, F D Duca, A K Kammerlander, A C Carpinteiro, H A Agis, G P Palladini, P M MilaniAbstract
Introduction
Cardiac immunoglobulin light-chain amyloidosis (AL-CA) requires rapid disease-specific hematologic treatment whereas the role of adjunctive heart failure (HF) management is unclear. This study aimed to evaluate prescription patterns and prognostic implications of conventional HF medication in a contemporary cohort of patients with AL-CA across multiple centers.
Methods
This large-scale international, multicenter cohort study included consecutive patients diagnosed with AL-CA between 2016 to 2024 across three European tertiary referral centers. Utilization of HF agents [renin–angiotensin system inhibitors (RASi), mineralocorticoid receptor antagonists (MRA), betablockers (BB)], dosages, and tolerability were recorded. Target trial emulation using inverse probability of treatment weighting (IPTW) accounted for differences in baseline risk profiles between patients with vs. without treatment and assessed implications of HF agents on time to first hospitalisation for heart failure (HFH) and/or death.
Results
A total of 708 patients (median 67 years, 35% female, 43% Mayo stage IIIA/B) were included. RASi, BB, and MRA were prescribed to 235 (33%), 321 (45%), and 248 (35%) patients, respectively, with significantly different frequencies across centers. Patients with vs. without BB and MRA treatment had more severe (more severe dyspnoea, worse systolic function, higher NT-proBNP, higher Mayo Stage) and those with RASi less severe cardiac involvement (lower NT-proBNP, better systolic function). RASi, BB, and MRA were prescribed at a median of 25% (IQR 20-50), 25% (IQR 12.5-50), and 50% (IQR 50-100) of the target heart failure dose, respectively. Hematologic response at 6-months among survivors (n=450) was complete in 29%, very good partial in 34%, partial in 9%, and none in 28%. Among 6-month survivors, RASi, BB, and MRA were reduced/discontinued due to hemodynamic intolerance in 25%, 6%, and 1%, respectively. After IPTW, RASi treatment was associated with a lower hazard for HFH/death (weighted hazard ratio 0.77; 95% CI 0.61 to 0.96), while no significant signals were found for BB/MRA.
Conclusion
Prescription of conventional heart failure medications is impacted by the severity of the cardiac phenotype and significantly differs across centers highlighting the lack of international consensus on utilization. HF agents, particularly RASi, are poorly tolerated hemodynamically by a significant proportion of patients. Treatment with RASi was linked to lower mortality hazard, but results need to be interpreted in the context of the non-randomised study setting and call for randomised trials to investigate the effectiveness and tolerability of supportive heart failure medication in AL-CA on top of disease-specific treatment.Heart failure medication in AL-CAFor image description, please refer to the figure legend and surrounding text.