More than 34% of 'red flags' found in patients consistent with a suspicion of hypertrophic cardiomyopathy (HCM) may be detected in a generalist setting, according to a study published Feb. 10 in European Heart Journal.

Niccolò Maurizi, BS, et al., looked at 818 patients diagnosed with HCM (62% male, mean age 49±21 years) referred to four European centers, with prespecified red flags organized into five domains for analysis: family history, physical examination, electrocardiography, echocardiography and laboratory. Overall, 39% of patients analyzed had a pathogenic or likely pathogenic sarcomere gene variant, 29% had a TTR and GLA variant, 19% had a syndromic cause, and 13% had no identifiable cause.

Clinical history or examination alone was sufficient for PCPs to detect 34% of the 2,979 red flags identified in the study cohort by the researchers. In the cardiologist's office, with access to diagnostic tools such as 12-lead electrocardiogram (ECG) and echocardiography, 66% of red flags were detected.

Age at diagnosis was a significant distinguishing factor. Among patients <20 and >60 years, non-sarcomeric etiologies were most often diagnosed. In adolescence (mean age 16±8 years), Danon disease, Friedreich's ataxia, Noonan syndrome and PRKAG2 cardiomyopathy were mainly diagnosed. In the neonatal/early childhood timeframe (mean age 3±2 years), syndromic diseases (RASopathies, inherited metabolic disorders, mitochondrial disorders) were most commonly diagnosed.

Furthermore, red flags detected by clinical history, physical examination and routine laboratory testing were most common in patients with HCM caused by RASopathies (48%), inherited metabolic disorders (47%) and mitochondrial disorders (57%). While physical red flags were almost exclusively seen in patients with a definite nonsarcomeric etiology (348/350), most red flags related to geno-positive and geno-negative HCM were detected via ECG and echocardiography (692/990 [70%] and 332/375 [88%], respectively).

"Based on our findings, the majority of non-sarcomeric etiologies of HCM can be suspected with a high degree of accuracy in a generalist setting," state the authors. This novel concept is essential, they note, to promote awareness of conditions too often considered confined to a 'super-specialist' setting, as well as for more appropriate use of diagnostic resources.

"While the ultimate diagnosis of a rare disease may be challenging outside tertiary centers," they write, "the role of systematic [red flag] collection remains key for timely referral and use of targeted therapies."