Cardiac Amyloidosis Mimicking Heart Failure With Preserved Ejection Fraction: Evaluating Self-Reported Red Flags in Routine Clinical Practice.

Background Cardiac amyloidosis is often underdiagnosed and can mimic heart failure with preserved ejection fraction (HFpEF), particularly in older adults. Most cases of cardiac amyloidosis are discovered in the late stages as a result of overlapping clinical symptoms. This study addresses whether patients with symptomatic heart failure and associated red flag features of cardiac amyloidosis have a worse functional status and quality of life than patients with classical HFpEF. Methodology This cross-sectional study was conducted between July 2024 and May 2025, in Lahore, Pakistan, in the cardiology departments of hospitals and clinics. Participants were recruited using a convenience method, in which 389 adults experiencing heart failure symptoms were interviewed. Data were collected using a structured, self-reported questionnaire that included demographic items, a seven-item checklist of red flag symptoms (e.g., carpal tunnel syndrome, unintentional weight loss, dizziness, and unexplained shortness of breath), and validated tools of physical limitations and quality of life. To assess the association between red flag symptoms and clinical outcomes, non-parametric statistical tests, correlation tests, and ordinal logistic regression were employed using SPSS Version 26 (IBM Corp., Armonk, NY, USA). Results Among 389 participants (mean age 51.4 ± 8.8 years), those with two or more red flags (suspected cardiac amyloidosis group) had significantly worse NYHA functional class scores (U = 954.500, p < 0.001) and lower quality of life scores (U = 580.000, p < 0.001) compared to typical HFpEF patients. The suspected cardiac amyloidosis group had a median New York Heart Association (NYHA) score of 3.00 (interquartile range (IQR) = 3.00-4.00) and a median quality of life score of 42.00 (IQR = 32.00-54.00). The red flag burden was positively correlated with worse functional status (r = 0.26, p < 0.01) and negatively correlated with quality of life (r = -0.32, p < 0.01). Logistic regression showed that poorer functional status and quality of life were significant predictors of suspected cardiac amyloidosis classification. Conclusions The results showed that an increase in the burden of red flag symptoms is linked to greater physical limitation and poorer quality of life among heart failure patients. Although no diagnostic imaging was conducted in this study, the symptom-based screening tool can complement echocardiographic vigilance in clinical practice, helping identify individuals at risk for cardiac amyloidosis who may benefit from further investigations. Further studies are necessary to validate these tools and analyze the ways of implementing them within the early referral process.