Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive disease that results from the accumulation of transthyretin (TTR) fibrils in the extracellular space of the myocardium, leading to heart failure.1 The pathogenesis of ATTR-CA results from a reduction in cardiac compliance due to amyloid fibril deposition, but recent observations suggest that soluble TTR intermediate oligomers are toxic to cardiomyocytes and contribute to myocardial functional compromise.2
Recently, proof-of-mechanism and proof-of-concept have been established for the ability of monoclonal antibodies to induce Fc gamma-mediated clearance of extracellular beta-amyloid in patients with Alzheimer's disease.3 This led to the Food and Drug Administration approval of a drug that clears amyloid plaques and attenuates cognitive decline.3 In pre-clinical studies, several monoclonal antibodies have been shown to mediate Fc gamma-dependent clearance of aggregated TTR by macrophages in experimental models.4-6 Very recently, an initial phase I study demonstrated the safety of this approach and provided initial hints of efficacy in reducing imaging-related pathology via magnetic resonance imaging and scintigraphy.7
In a recent preliminary observation, antibodies binding to TTR were described for the first time in two patients with ATTR-CA, and were associated with spontaneous clinical recovery and regression of imaging-related findings.8 However, this intriguing finding has not yet established a mechanistic role for these naturally occurring antibodies in facilitating amyloid removal.
We aimed to characterize in detail the spontaneously occurring purified antibodies to TTR oligomers and fibrils and test their related functional activities in vitro and in cellular and experimental models, supporting their potential involvement in the spontaneous regression of ATTR amyloidosis.
Aims: Heart failure (HF) is a leading cause of hospitalization, and sex differences in care have been described. We assessed sex-specific clinical outcomes and healthcare resource utilization following hospitalization for HF.
Methods and results: This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals in the Patient-Centered Care Transitions in HF (PACT-HF) cluster-randomized trial. The primary outcome was all-cause mortality. Secondary outcomes included all-cause readmissions, HF readmissions, emergency department (ED) visits, and healthcare resource utilization. Outcomes were obtained via linkages with administrative datasets. Among 4441 patients discharged alive, 50.7% were female. By 5 years, 63.6% and 65.5% of male and female patients, respectively, had died (p = 0.19); 85.4% and 84.4%, respectively, were readmitted (p = 0.35); and 72.2% and 70.9%, respectively, received ED care without hospitalization (p = 0.34). There were no sex differences in mean [SD] number of all-cause readmissions (males, 2.8 [7.8] and females, 3.0 [8.4], p = 0.54), HF readmissions (males, 0.9 [3.6] and females, 0.9 [4.5], p = 0.80), or ED visits (males, 1.8 [11.3] and females, 1.5 [6.0], p = 0.24) per person. There were no sex differences in mean [SD] annual direct healthcare cost per patient (males, $80 334 [116 762] versus females, $81 010 [112 625], p = 0.90), but males received more specialist, multidisciplinary HF clinic, haemodialysis, and day surgical care, and females received more home visits, continuing/convalescent care, and long-term care. Annualized clinical events were highest in first year following index discharge in both males and females.
Conclusions: Among people discharged alive after hospitalization for HF, there were no sex differences in total and annual deaths, readmissions, and ED visits, or in total direct healthcare costs. Despite similar risk profiles, males received relatively more specialist care and day surgical procedures, and females received more supportive care.
Clinical trial registration: ClinicalTrials.gov NCT02112227.
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