Does a heart to contralateral lung ratio of 1.1 indicate myocardial involvement in a patient with potential risk factors such as hypertension, chronic kidney disease, or a family history of amyloidosis?

H/CL Ratio of 1.1 Does NOT Confirm Myocardial Involvement

A heart-to-contralateral lung (H/CL) ratio of 1.1 is below the diagnostic threshold and does not confirm ATTR cardiac amyloidosis or myocardial involvement. This ratio falls well below the required cutoffs of ≥1.5 at 1 hour or ≥1.3 at 3 hours, and critically, diagnosis cannot be made based on H/CL ratio alone without visual confirmation of diffuse myocardial uptake on SPECT imaging 1.

Critical Diagnostic Requirements

The 2021 ASNC/AHA/ASE expert consensus establishes a stepwise diagnostic algorithm that must be followed 1:

Step 1: Visual Confirmation on SPECT (Mandatory First Step)

• SPECT imaging must first confirm diffuse myocardial radiotracer uptake before any H/CL ratio interpretation is valid 1
• The H/CL ratio is not recommended if there is absence of myocardial uptake on SPECT 1
• Differentiation from residual blood pool activity, focal myocardial infarction, and overlapping bone uptake is required on SPECT 1
• If excess blood pool activity is present at 1 hour, repeat SPECT imaging at 3 hours to maximize specificity 2

Step 2: Visual Grading System (0-3 Scale)

After confirming myocardial uptake on SPECT, grade the uptake relative to ribs 1:

• Grade 0: No myocardial uptake (normal bone uptake) - NOT consistent with ATTR-CA
• Grade 1: Myocardial uptake less than rib uptake (equivocal, requires further evaluation)
• Grade 2: Myocardial uptake equal to rib uptake (diagnostic for ATTR-CA if monoclonal protein excluded)
• Grade 3: Myocardial uptake greater than rib uptake with mild/absent rib uptake (diagnostic for ATTR-CA if monoclonal protein excluded)

Step 3: H/CL Ratio (Only When Applicable)

The H/CL ratio serves a limited, adjunctive role 1:

• H/CL ≥1.5 at 1 hour is diagnostic for ATTR-CA (when myocardial uptake confirmed on SPECT and AL amyloidosis excluded) 1
• H/CL ≥1.3 at 3 hours is diagnostic for ATTR-CA 1
• Your ratio of 1.1 is below both thresholds and does not meet diagnostic criteria
• H/CL ratio is most useful when visual grade is equivocal (Grade 1 vs Grade 2) to help classify as positive or negative 1, 2
• If visual grade is 2 or 3, diagnosis is confirmed and H/CL ratio assessment is not necessary 1

Common Pitfalls and Critical Warnings

False Positive Risk

• Incorrect diagnosis of ATTR-CA based on planar imaging and H/CL ratio without SPECT confirmation of diffuse myocardial uptake has been observed at multiple sites 2
• This leads to inappropriate therapy and worse patient outcomes 2
• Excess blood pool activity on 1-hour images can be misinterpreted as positive scans 2

The Quantitative Approach Limitation

Research demonstrates that the H/CL approach results in a significantly higher proportion of equivocal studies (66% equivocal) compared to the semi-quantitative visual grading approach (8% equivocal) 3

• The visual grading system using SPECT minimizes equivocal results and shows high concordance at both 1 and 3 hours 3
• In cases where H/CL and visual grading were discordant, biopsy results were concordant with the SPECT visual grade, not the H/CL ratio 3

Mandatory AL Amyloidosis Exclusion

Even if imaging were positive, all patients with suspected cardiac amyloidosis must undergo screening for monoclonal plasma cell dyscrasia before confirming ATTR-CA diagnosis 1, 2:

• Obtain serum and urine immunofixation electrophoresis
• Obtain serum free light chain assay
• Grade 2 or 3 uptake can be seen in >20% of patients with AL cardiac amyloidosis 1
• Missed diagnosis of AL amyloidosis occurs when these studies are not recommended in the PYP report 2

Other Causes of Myocardial Uptake

99mTc-PYP/DPD/HMDP uptake can occur in other causes of myocardial injury 1:

• Pericarditis
• Myocardial infarction (regional uptake pattern)
• Chemotherapy or drug-associated myocardial toxicity

Next Steps for This Patient

Given the H/CL ratio of 1.1 with only planar imaging provided:

1. Review the SPECT images (if performed) to determine if there is any diffuse myocardial uptake visually 1, 2
2. If SPECT was not performed, it must be obtained to properly interpret this study 2
3. If SPECT shows no myocardial uptake (Grade 0), this study is negative for ATTR-CA 1
4. If SPECT shows Grade 1 uptake, the study is equivocal and requires further evaluation to exclude AL amyloidosis 1
5. Consider cardiac MRI if clinical suspicion remains high despite negative scintigraphy 2
6. Consider referral to an amyloidosis expert when imaging is equivocal or discordant with clinical findings 2