Genetic testing is the step most often omitted once a cardiomyopathy has been characterized and most often misapplied when extended to people who have no phenotype, as illustrated by a case of transthyretin amyloid cardiomyopathy presenting without classic red flags.
Key Findings
Results
A 68-year-old African American man was diagnosed with transthyretin amyloid cardiomyopathy (ATTR-CM) despite presenting without any of the classic clinical red flags associated with the condition.
The patient was 68 years old and African American, a demographic with known elevated prevalence of the Val122Ile (p.Val142Ile) TTR variant.
The case illustrates that the absence of classic red flags does not exclude ATTR-CM and should not preclude genetic testing when the phenotype is present.
The case is used to define who should be tested, what must be excluded first, and what the result changes clinically.
Background
Genetic testing is most often omitted after a cardiomyopathy has been characterized and most often misapplied when extended to individuals without a phenotype.
The author identifies two principal errors in current practice: under-testing in phenotype-confirmed cardiomyopathy and over-testing in the absence of any phenotype.
The paper frames appropriate genetic testing as requiring a confirmed phenotype as a prerequisite.
The case is used as a vehicle to define the correct indications and sequencing of genetic evaluation in heart failure and cardiomyopathy.
Discussion
The paper defines a framework for genetic testing in cardiomyopathy that specifies who should be tested, what must be excluded first, and what the result changes.
The framework is built around the case of ATTR-CM presenting without classic red flags.
The author emphasizes that exclusion of alternative diagnoses is a necessary step before genetic testing is applied.
The clinical utility of genetic testing is framed in terms of what the result changes in management or family implications.
What This Means
This research describes the case of a 68-year-old African American man who was diagnosed with a heart condition called transthyretin amyloid cardiomyopathy (ATTR-CM), a disease where a protein called transthyretin misfolds and deposits in the heart. What made this case notable is that he had none of the warning signs doctors are typically taught to look for when suspecting this diagnosis. The author uses this case to highlight a widespread problem in clinical practice: genetic testing is frequently skipped after a heart muscle disease has already been identified, and at the same time it is frequently ordered inappropriately in people who have no signs of disease at all.
This research suggests that the presence of a confirmed heart muscle disease (phenotype) — not the presence or absence of specific warning signs — should guide the decision to pursue genetic testing. The author argues that before genetic testing is ordered, other potential causes of the cardiomyopathy should be ruled out, and that the value of testing should be judged by whether the result would actually change the patient's care or have implications for family members.
The practical importance of this paper lies in its challenge to the assumption that classic red flags must be present to justify genetic testing in cardiomyopathy. For a condition like ATTR-CM, which has treatments available and has elevated prevalence of a specific genetic variant in African Americans, missing the diagnosis because red flags are absent could mean missing a treatable cause of heart failure. The paper calls for a more systematic and indication-driven approach to genetic testing in cardiology.
Bakr Salama A. (2026). The Red Flags Were Missing, the Indication Was Not: Genetic Testing in Heart Failure and Cardiomyopathy.. Methodist DeBakey cardiovascular journal. https://doi.org/10.14797/mdcvj.1955