Transthyretin Cardiac Amyloidosis: Presentation Across the LVEF Spectrum

Researchers at the Cleveland Clinic in Florida presented new insights on the spectrum of transthyretin cardiac amyloidosis (ATTR-CA) at the 2024 International Symposium on Amyloidosis. Led by Dipan Uppal and colleagues, the study investigates the prevalence and implications of ATTR-CA across different heart failure phenotypes, highlighting the importance of recognizing this condition in patients with varying ejection fractions.

ATTR-CA is typically associated with heart failure with preserved ejection fraction (HFpEF). However, the incidence and impact of ATTR-CA in patients with lower ejection fractions are less well-characterized. This study aims to address this gap by examining the prevalence and clinical characteristics of ATTR-CA in patients with heart failure with reduced (HFrEF) and mid-range (HFmrEF) ejection fractions.

Investigators set out to explore the spectrum of heart failure phenotypes and left ventricular function in patients with known ATTR-CA. This single-center, retrospective, cohort study included 213 consecutive patients diagnosed with ATTR-CA at the Cleveland Clinic in Florida between February 2016 and December 2022. Data on patient demographics, comorbidities, imaging, and laboratory findings were collected and analyzed.

The mean age of the cohort was 78.1 years, with a predominance of male patients (91.1%). At diagnosis, 21.6% had HFrEF, 17.8% had HFmrEF, and 60.6% had HFpEF. Common comorbidities included hypertension (78.9%), ischemic heart disease (55.9%), atrial fibrillation (72.8%), and chronic kidney disease (63.4%).

Patients with HFrEF or HFmrEF had worse symptoms, with a higher proportion in New York Heart Association functional class III or IV (71.7% and 52.6%, respectively) than those with HFpEF (42.9%). Additionally, these patients had higher NT-proBNP levels and serum creatinine, indicating more severe heart failure and renal dysfunction.

The mean left ventricular ejection fraction (LVEF) varied significantly across the phenotypes: 33.5% in HFrEF, 45.4% in HFmrEF, and 56.8% in HFpEF. End-diastolic left ventricular internal diameter expectedly increased as LVEF decreased, reflecting more severe ventricular remodeling in patients with lower ejection fractions.

This study broadens the understanding of the phenotypic spectrum of ATTR-CA. While ATTR-CA is thought primarily to manifest with HFpEF and restrictive cardiomyopathy, 2 in 5 patients with ATTR-CA in this cohort had reduced or mid-range LVEF. Moreover, these patients were sicker overall, indicating a more advanced stage of heart failure. The data suggest that clinicians should maintain a high index of suspicion for ATTR-CA in heart failure patients, irrespective of their ejection fraction, to improve diagnosis and optimize therapeutic strategies.

Key Takeaways

– ATTR-CA may be more prevalent in patients with HFrEF and HFmrEF than traditionally recognized, necessitating heightened clinical suspicion across all ejection fraction categories.

– ATTR-CA patients with lower ejection fractions (HFrEF and HFmrEF) exhibit more severe symptoms and greater functional impairment compared with those with HFpEF.

– The findings underscore the importance of considering ATTR-CA in the differential diagnosis of heart failure, regardless of ejection fraction, to ensure appropriate management and treatment.