Wild-type transthyretin amyloidosis patients exhibited significant impairment in heart rate and blood pressure regulation during orthostatic challenges and a pathological Valsalva ratio in 83% versus 30% in controls, despite similar autonomic symptom questionnaire scores.
Observational (n=40)
No
Patients with wild-type transthyretin amyloidosis exhibit significant cardiovascular autonomic dysfunction, particularly cardiac parasympathetic and sympathetic adrenergic impairment, which may mimic heart failure symptoms and complicate pharmacological management.
Effect estimate: p=0.394 for COMPASS 31 total score (no significant difference)
Absolute Event Rate: 8.6% vs 6.4%
p-value: p=0.001 for heart rate and p=0.010 for systolic BP during passive orthostatic challenge; p=0.001 HR and p=0.002 systolic BP during active orthostatic challenge; p=0.020 for pathological Valsalva ratio (83% vs 30%)
Abstract Background Autonomic dysfunction is well recognized in hereditary transthyretin amyloidosis (ATTRv), but it has not been systematically studied in wild-type transthyretin amyloidosis (ATTRwt). Because ATTRwt primarily presents with cardiomyopathy, autonomic symptoms may mimic heart failure and lead to inappropriate treatment. Here we aimed to investigate the presence and extent of autonomic dysfunction in ATTRwt. Methods In ATTRwt patients and controls, we performed an extensive autonomic examination, including standardized questionnaires, passive and active orthostatic challenges, Valsalva maneuver, deep breathing and sudomotor assessment. Results 20 ATTRwt patients and 20 controls were included. Composite Autonomic Symptom Score 31-scores were similar between the groups. Orthostatic challenges revealed impaired blood pressure (BP) and heart rate regulation in ATTRwt compared to controls (for passive orthostatic challenge: HR p = 0.001, systolic BP p = 0.010) and diastolic BP p = 0.006; for active orthostatic challenge: HR p = 0.001, systolic BP p = 0.002, diastolic BP p = 0.002). A lack of late phase 2 BP overshoot during Valsalva maneuver was observed in ATTRwt and Valsalva Ratio was pathological in 83% of ATTRwt versus 30% of controls ( p = 0.020). The rate of pathological sweat tests did not differ between ATTRwt patients and controls. Conclusions Autonomic symptoms in ATTRwt were infrequently reported. However, detailed assessment revealed cardiovascular autonomic dysfunction, which contributes to the overall clinical phenotype of ATTRwt.
Kleinveld et al. (Sun,) conducted a observational in Elderly patients (mean age 78) with wild-type transthyretin amyloidosis cardiomyopathy versus age-matched healthy controls (n=40). Detailed autonomic function testing including COMPASS 31 questionnaire, orthostatic challenges, Valsalva maneuver, deep breathing test, and sudomotor function tests vs. Age-matched healthy controls was evaluated on Cardiovascular autonomic dysfunction assessed by orthostatic challenges (heart rate and blood pressure regulation), Valsalva maneuver parameters (BP overshoot and Valsalva ratio), and COMPASS 31 symptom score (p=0.394 for COMPASS 31 total score (no significant difference), p=p=0.001 for heart rate and p=0.010 for systolic BP during passive orthostatic challenge; p=0.001 HR and p=0.002 systolic BP during active orthostatic challenge; p=0.020 for pathological Valsalva ratio (83% vs 30%)). Wild-type transthyretin amyloidosis patients exhibited significant impairment in heart rate and blood pressure regulation during orthostatic challenges and a pathological Valsalva ratio in 83% versus 30% in controls, despite similar autonomic symptom questionnaire scores.