Holter Recordings at Initial Assessment for Long QT Syndrome: Relationship to Genotype Status and Cardiac Events

Abstract

Background: The relationship of Holter recordings of repolarization length to outcome in long QT syndrome (LQTS) is unknown. Methods: Holter recordings and initial 12 lead ECG QTc were related to outcome in 101 individuals with LQTS and 28 gene-negative relatives. Mean QTc (mQTc) and mean RTPc (R-wave to peak T-wave, mRTPc) using Bazett correction were measured, analyzing heart rates 40 to 120 bpm. Previously reported upper limit of normal (ULN) were: women and children (<15 years), mQTc 454, mRTPc 318 ms; men mQTc 446 ms, mRTPc 314 ms. Results: Measurements in LQTS patients were greatly prolonged; children and women mean mQTc 482 ms (range 406−558), mRTPc 351 ms (259−443); males > 15 years mQTc 469 ms (407−531), mRTPc 338 ms (288−388). Ten patients had cardiac arrest (CA), and 24 had arrhythmic syncope before or after the Holter. Holter values were more closely related to genotype status and symptoms than 12 lead QTc, e.g., sensitivity/specificity for genotype positive status, mRTPc > ULN (89%/86%); CA, mRTPc > 30 ms over ULN (48%/100%). Of 34 symptomatic (CA/syncope) patients, only 9 (26%) had 12 lead QTc > 500 ms, whereas 33/34 (94%) had an mRTPc or mQTc above ULN. In 10 with CA, all Holter measurements were > 15 ms above ULN, but only two had 12 lead QTc > 500 m. Conclusions: Holter average repolarization length, particularly mRTPc, reflects definite LQTS status and clinical risk better than the initial 12 lead QTc. Values below ULN indicate both a low risk of having LQTS and a low risk of cardiac events in the small percentage that do.

Keywords: Holter monitor; diagnosis; long QT syndrome; risk stratification.

Figure 1

Holter-derived mean QTc (Panel (A)) and RTPc values (Panel (B)) from 101 subjects with long QT syndrome, values are mean ± SD (ms, milliseconds). “Girls”—females < 15 years and “Boys”—males < 15 years. Normative ranges are shown in grey shading. The central motif indicates the mean value.

Figure 2

The association of ECG and Holter recording measurements with symptoms and cardiac arrest among families presenting for assessment with long QT syndrome (101 patients with long QT syndrome and 28 gene negative family members). (A) Panel shows QTc values from the initial 12 lead ECG expressed as milliseconds above the age/sex-based reference values. Only 2/10 patients who had cardiac arrest (left side) and 7/24 symptomatic patients (right side) had a QTc exceeding 500 ms on their first ECG. (B) This panel shows Holter-derived mean RTPc values (R wave to peak T wave corrected for heart rate) expressed as milliseconds above the age/sex-based reference range. Results from 10 cardiac arrest survivors are shown on the left versus the rest, and on the right the symptomatic versus asymptomatic subjects are shown. Only one symptomatic patient had a value in the normal range. ms = milliseconds. Black circle—LQTS with symptoms, black square—LQTS with cardiac arrest, white circle—all subjects (gene positive and negative) without symptoms, white square—all subjects (gene positive and negative) without cardiac arrest.

Figure 3

Holter-derived mean QTc and RTPc values are shown from those less than 7 years of age. Normative controls (n = 16) are shown in grey, and those with long QT syndrome (n = 31) are shown in black. Values were rounded up or down to the nearest 10 ms.