Impaired autonomic control of heart interval changes to Valsalva manoeuvre in Chagas' disease without overt manifestation

Abstract

Background: In the apparent indeterminate form of Chagas' disease, which lacks any overt clinical, electrocardiographic, and radiological manifestations of organ damage, lesions of the intrinsic autonomic innervation of heart are not striking features and evidences for cardiac autonomic dysfunction are elusive and conflicting. Objective: To evaluate the cardiac autonomic modulation based on Valsalva manoeuvreassociated heart interval variation in Chagas' disease subjects with apparent indeterminate form. Subjects and methods: We examined 36 outpatient volunteers aged 15 -51 years old (median: 36.5), in comparison with 52 healthy control individuals aged 17 -49 years old (median: 29) ( p < 0.001). Each subject sequentially performed in the supine position three to four manoeuvres at an intra-oral pressure of 40 mm Hg during 20 s, under continuous DII lead electrocardiographic registration, and rate-and time-dependent indices of Valsalva manoeuvre-associated R -R interval variation were obtained. The t-test or the Mann -Whitney test was employed to compare the data between the groups. Results: No correlation was found between every index and age for the control group ( p = 0.39 -0.71). The chagasic group presented similar basal to phase IV median increment (relative bradycardia) (23.7% vs. 22.7%; p = 0.63) and smaller basal to phase III median decrement of R -R interval (relative tachycardia) ( À 31.7% vs. À 35%; p = 0.02) in comparison to the control group, respectively. The median Valsalva ratio showed a tendency for reduction in chagasics (1.78 vs. 1.90; p = 0.08). Prolonged median time (14.2 vs. 10.3 s; p < 0.001) and slowed median velocity (5.1%/s vs. 8.9%/s; p < 0.001) of the phases III -IV bradycardia were also observed in chagasic group. The majority (58.3%) of the chagasics presented exclusively at least one depressed, and 8.3% presented at least one enhanced index of rateand/or time-dependent heart interval responses beyond the 25th or 75th control percentiles, and 27.8% presented at least one depressed and other enhanced index, while 5.6% showed all indices within the control interquartile range. All the indices outside the 25th or 75th control percentiles were noted in 13.9% of chagasics. Conclusion: Chagas' disease subjects without overt manifestations presented variable and subtle depression and less frequent enhancement or normality of the rate-and time-dependent tachycardia and bradycardia reflex responses related to Valsalva manoeuvre, which demonstrates distinct patterns of finely disturbed cardiac sinus parasympathetic and sympathetic modulation, probably due to inflammatory or autoimmunological damage of intrinsic innervation and/or to autoantibodies-induced derangement in neurotransmitter receptors. D

Estresse ortostático ativo e arritmia sinusal respiratória em chagásicos com função sistólica global do ventrículo esquerdo preservada

“…The active orthostatic stress test is sensitive, specific, reproducible, and easily performed, being con- Table I The results of the active orthostatic stress test in chagasic patients with no heart disease, as compared with that in normal controls, confirm the findings of our previous study performed in the same group of patients [4][5][6] , and in another sample later studied 7,8 , and also the findings reported by other authors [24][25][26][27] . The different methods used, such as the variability in heart rate (assessed with different techniques) 5,7,8,22 , the Valsalva maneuver 6,23,24,26 , and respiratory sinus arrhythmia 5,26 , showed that autonomic dysfunction is present in patients with no evidence of heart disease and with preserved left ventricular function. The set of these results definitively answers a question that has pervaded the literature during the last 2 decades: whether autonomic dysfunction precedes or not left ventricular dysfunction in Chagas' disease [26][27][28][29][30] .…”

Muscarinic antibodies and heart rate responses to dynamic exercise and to the Valsalva maneuver in chronic chagasic patients

“…These investigations have demonstrated that, the chronotropic responses to cardiac autonomic tests are apparently impaired in the indeterminate form of the disease. However, we [7][8][9]20,21,37 and other investigators 16 have found that chagasic patients who are in different stages of natural history of the disease may have normal, abnormal 2 or even enhanced responses to conventional cardiac autonomic tests 15,27 . Moreover, the frequency and time domain indexes of parasympathetic modulation may be suppressed in the supine position, but become similar to controls in the standing position and while performing isometric exercise 6,24,27,45 .…”

“…However, we [7][8][9]20,21,37 and other investigators 16 have found that chagasic patients who are in different stages of natural history of the disease may have normal, abnormal 2 or even enhanced responses to conventional cardiac autonomic tests 15,27 . Moreover, the frequency and time domain indexes of parasympathetic modulation may be suppressed in the supine position, but become similar to controls in the standing position and while performing isometric exercise 6,24,27,45 . Since, muscarinic auto-antibodies may behave as positive allosteric modulators of parasympathetic activity 25 ; a diminished high frequency component of heart rate variability 41 and the presence of a slow heart rate 44 could be an indirect expression of the agonist effect.…”

“…Parasympathetic effects on heart rate, of asymptomatic chagasic patients who are in the indeterminate and cardiac stages of the disease, have been studied under stressful 2,20,27 , and under steady-state conditions 6,24,45 . The findings of these clinical investigations have been conflicting and controversial.…”

Mechanisms of pathogenesis in Chagas disease

“…However, other studies have shown cardiac autonomic function to be essentially normal in patients with indeterminate Chagas disease but abnormal in patients presenting overt cardiac disease (Caeiro et al 1980, Junqueira et al 1985, Junqueira and Soares 2002. These observations appear to oppose the tenets of the neurogenic hypothesis, since parasympathetic alterations do not seem to be a significant factor in Chagas disease prior to the onset of the chronic phase (Davila et al 1989(Davila et al , 1998.…”