Amyloid-targeted PET after negative or low-grade bone scintigraphy for cardiac amyloidosis: a systematic review

To assess myocardial positron emission tomography (PET) positivity after negative or low-grade bone scintigraphy, while distinguishing test discordance from independently confirmed cardiac amyloidosis. PubMed, Scopus and Web of Science were searched through 5 August 2026, with targeted source assessment through 2 October 2026. Negative and low-grade imaging denoted Perugini grades 0 and 1, respectively; study-defined negative results were described separately. Eligibility required linked PET and bone-scan results with an extractable denominator. Acquisition modality, PET thresholds and cardiac reference standards were examined. A restricted synthesis required documented tomographic acquisition; a broader three-report synthesis was exploratory. Nine reports provided extractable paired results. In the hereditary transthyretin subgroup examined with carbon-11 Pittsburgh compound B, 20/23 participants were PET-positive after excluding one acquired, domino-transplant case. The exploratory pooled proportion was 87.0% (95% profile-likelihood confidence interval, 68.5–97.8%). Restriction to clearly documented cohort-wide tomography retained only two reports, precluding the planned pooled analysis. Uptake definitions and cardiac verification differed substantially. General diagnostic studies without complete bone-grade denominators, including REVEAL, were excluded from the eligible synthesis and retained as context. PET positivity is common in selected hereditary transthyretin cohorts with negative or low-grade bone scans, but does not establish cardiac amyloidosis or earlier diagnosis. Conditional diagnostic accuracy remains unresolved. Prospective paired studies require tomographic localization, tracer-specific thresholds and independent cardiac verification.