Novel electrocardiographic criteria may render possible the more accurate recognition of cardiac amyloidosis

Aims The early diagnosis of cardiac amyloidosis (CA) is paramount, since there are effective therapies that improve patient survival. The diagnostic accuracy of classical electrocardiographic (ECG) signs, such as low voltage, pseudoinfarct pattern, and conduction disturbances in the diagnosis of CA, is inferior to that of the echocardiographic myocardial deformation criteria; therefore, our aim was to find more accurate novel ECG criteria for this purpose. Methods We tested the diagnostic value of five novel ECG criteria, two of them devised by us, in 34 patients with confirmed CA (20 transthyretin amyloidosis and 14 AL amyloidosis) and 45 control patients with left ventricular hypertrophy on echocardiography due to hypertension, valvular aortic stenosis and hypertrophic cardiomyopathy. The following novel ECG criteria, that suggested CA, were tested: QRS amplitude in lead I < 0.55 mV (I < 0.55); QRS amplitude in lead aVR < 0.5 mV (aVR < 0.5); average QRS amplitude of leads I + aVR < 0.575 mV [(I + aVR) < 0.575]; average QRS amplitude of leads I + aVR/average QRS amplitude of leads V 1–4 < 0.375 [(I + aVR)/(V 1–4 ) < 0.375]; average QRS amplitude of leads I + aVR/longest intrinsicoid deflection in leads I,aVL,V 1–6 < 0.0115 [(I + aVR)/I,aVL,V 1–6 ID < 0.0115]. Results The I < 0.55, aVR < 0.5, (I + aVR) < 0.575, (I + aVR)/(V 1–4 ) < 0.375, (I + aVR)/I,aVL,V 1–6 ID < 0.0115 test accuracy (TA) were 81%, 84.8%, 82.3%, 84.8%, and 83.3%, respectively; the sensitivity (SE): 76.5%, 82.4%, 85.3%, 82.4%, and 76.9%; specificity (SP): 84.4%, 86.7%, 80%, 86.7%, and 87.5%; positive predictive values (PPV): 78.8%, 82.4%, 76.3%, 82.4%, and 80%; negative predictive values (NPV): 82.6%, 86.7%, 87.8%, 86.7%, and 85.4%; area under curve (AUC) values: 0.8922, 0.8794, 09016, 0.8824, and 0.8462 were respectively. These parameters of the novel ECG criteria were at least as good as those reported by other authors in the literature of the qualitative (TA: 67%, SE: 80%, SP: 34%, PPV: 75%, NPV: 42%, AUC: 0.57) and quantitative apical sparing (TA: 64–80%, SE: 66–81.3%, SP: 55–78.3%, PPV: 33–83.9%, NPV: 41–75%, AUC: 0.62–0.68) and left ventricular ejection fraction/global longitudinal strain >4.1 (TA: 77%, SE: 93%, SP: 38%, PPV: 79%, NPV: 69%, AUC: 0.65) echocardiographic criteria. Among the classical criteria, the low voltage in limb leads criterion was present most frequently (in 73.5%) in patients with CA, with slightly worse diagnostic value than the novel ECG criteria (TA: 78.5%, SE: 73.5%, SP: 82.2%, PPV: 75.8%, NPV: 80.4%). Conclusions The novel ECG criteria [mostly the aVR < 0.5, (I + aVR)/(V 1–4 ) < 0.375] seem at least as reliable in the diagnosis of CA as the best echocardiographic myocardial deformation criteria and might be used either together with the echocardiographic criteria or as stand‐alone criteria to diagnose CA in the future.