Electrocardiographic Measures and Heart Rate Variability in Patients with Familial Dysautonomia

Abstract

Cardiovascular abnormalities are prominent in the genetic disorder, familial dysautonomia (FD). To determine if autonomic dysfunction involves cardiac, as well as peripheral vascular integrity, noninvasive tests were performed in 10 FD patients and 8 healthy control subjects while supine and at 90° tilt. Simultaneous blood pressure (BP) and heart rate (HR) and QTc were obtained, while performing signal-averaged electrocardiography (SAECG) and heart rate variability (HRV). FD subjects were tested on 2 separate days, before and 1 h after oral fludrocortisone or midodrine; controls were tested once without medication. With tilt, all FD subjects decreased mean BP > 24 mm Hg by 5 min. On SAECG, 70% of supine FD subjects had a prolonged tQRS; only 2 FD subjects shortened tQRS with tilt. The QTc interval was prolonged ( > 440 ms) in 2 supine FD subjects; with tilt, the QTc prolonged in a third. Frequency domain analysis of HRV revealed that mid (MF) and high frequency band areas were significantly decreased when supine, but not when upright. On time domain analysis, the pNN50 was significantly decreased in FD subjects (8.9 ± 1.7 vs. 17.7 ± 3.6%, p < 0.01). Fiudrocortisone lowered supine BP and HR and increased supine MF area. Midodrine raised supine and erect BP, lowered erect HR, and shortened erect QTc. Although all FD subjects have abnormal orthostatic BP and HR responses, cardiac tone, as assessed by electrocardiographic and HRV responses, varies. Prolongation of the tQRS appears to be a sensitive but not specific indicator of autonomic dysfunction. QTc prolongation may indicate more extensive sympathetic dysfunction. HRV data suggest some FD patients have abnormalities in parasympathetic, as well as sympathetic, cardiac tone.

Quantitative sensory testing of thermal and vibratory perception in familial dysautonomia

“…Clinically, some adult patients have experienced worsening peripheral sensory dysfunction, gait disturbances, and neuropsychological changes [2,42]. In addition, sympathovagal balance becomes more precarious with worsening of orthostatic hypotension, development of supine hypertension, and even occasional bradyarrhythmias [43]. There is a high mortality rate [26,44].…”

Pacemakers in patients with familial dysautonomia

“…FD patients do not exhibit consistent electrocardiographic findings. However, it has been suggested that prolongation of the tQRS may be a sensitive but not specific indicator of autonomic dysfunction and that QTc prolongation, and more specifically JTc prolongation, may be an ominous sign since there is a correlation with syncope [9,16,17]. The corrected QT interval (QTc) is modified by autonomic tone.…”

“…There have been studies that have attempted to correlate syncope with electrocardiographic changes [9,16,17]. Glickstein et aldemonstrated a higher prevalence of prolonged QTc in FD patients than in normal controls and a significantly higher prevalence of JTc prolongation than controls, especially in FD patients with syncope [16,17].…”

Electrocardiographic repolarization abnormalities in familial dysautonomia: an indicator of cardiac autonomic dysfunction

“…More recently, it has become apparent that FD patients are also at risk for cardiac rhythm abnormalities and may have dysfunctional mechanisms of intrinsic cardiac regulation. Upon review of the records of 513 FD patients presently registered with the Dysautonomia Treatment and Evaluation center, nine patients required pacemakers, six for bradycardia and syncope and three for complete heart block with asystole [11]. Retrospective analysis of cause of death in patients with FD [12] revealed 23% of the total group had unexplained "sleep death" and 17% had sudden daytime cardiorespiratory arrest.…”