Vagal Heart Rate Control in Patients with Atrial Fibrillation: Impact of Tonic Activation of Peripheral Chemosensory Function in Heart Failure

Abstract

Heart failure (HF) and atrial fibrillation (AF), emerging as two epidemics of the twenty-first century, are commonly associated with each other. Both have been mechanistically linked to changes in cardiac vagal control. The importance of peripheral chemosensors, located in the carotid body, has not been elucidated so far. We therefore investigated whether tonic activation of excitatory chemoreceptor afferents contributes to the altered vagal control in HF patients with a history of AF. In 18 patients (72 ±9 year, 7 male) with sinus rhythm and a history of AF (n=9, without any evidence of structural heart disease, AF group; n=9 with structural heart disease and clinical presentation of HF, AFHF group) we investigated the impact of chemosensory deactivation (by breathing 100% oxygen) on heart rate, blood pressure, cardiac output, total peripheral resistance, oxygen saturation and breathing rate. Ten healthy individuals served as a control group. In addition, we performed a deep breathing test demonstrating an impaired heart rate variation in patients with and without HF as compared with controls (expiration/inspiration difference: 23.9±6.9 vs. 6.9±6.1 bpm, and 23.9±6.9 vs. 7.8±4.8 bpm; p<0.05). In both control and AF groups, heart rate decreased during chemoreceptor deactivation (control: -4.8±3.4%; AF: -5.1±3.0%; p<0.05), whereas heart rate did not change in AFHF patients. This resulted in impaired cardiac chemoreflex sensitivity in AFHF patients (1.9±1.6 vs. 0.5±1.2 ms/mmHg; p<0.05). In conclusion, our data suggest that tonic activation of excitatory chemoreceptor afferents contributes to a low vagal tone in heart failure patients with a history of AF (Clinical Trials NCT01262508).

Sympathetic and Parasympathetic Coactivation Induces Perturbed Heart Rate Dynamics in Patients with Paroxysmal Atrial Fibrillation

“…Three tests were used to assess basal autonomic outflow, according to international consensus [ 24 – 26 ]: 1) Deep breathing test with calculation of the expiratory-inspiratory HR difference (E-I difference) and the expiratory-inspiratory HR ratio (E/I ratio) [ 16 , 27 , 28 ]. 2) Active standing test with calculation of the HR response to postural change (ratio of cycle lengths at beats 15 and 30 after standing; 30/15 ratio) [ 29 , 30 ].…”

Central Chemoreflex Sensitivity and Parasympathetic Nervous Activity in patients with Heart Failure

“…On the other hand, Giannoni et al (2009) [7] found CCS exacerbation in 23% of HF patients who have presented low functional capacity, low parasympathetic nervous activity, as well as high prevalence of paroxysmal atrial fibrillation and ventricular tachycardia. Accordingly, findings in the present study may have been influenced by the exclusion of patients with atrial fibrillation, since previous studies have shown that patients with chemoreflex exacerbation have higher prevalence of atrial fibrillation [16,17], as well as that atrial fibrillation in HF patients may be associated with reduced vagal modulation of HR [16,18], which leads to increased cardiac arrhythmic events [19] and heart failure-associated mortality rates [20].…”

“…HF patients were screened based on echocardiographic examinations performed at local reference centers in cities located in Rio Grande do Sul State, Brazil, from 2014 to 2018. Eighteen (18) assessed chronic obstructive pulmonary disease were excluded from the study [25]. Healthy and physically active individuals reporting smoking habit were also excluded from the study.…”

Respiratory sinus arrhythmia is reduced after pulmonary vein isolation in patients with paroxysmal atrial fibrillation

“…Supporting this, RSA is known to be reduced after atropine application in healthy humans [ 23 , 24 ] and is modulated in diseases such as diabetic autonomic neuropathy [ 25 , 26 ]. Although RSA also depends on feedback regulation such as chemoreceptors [ 27 ] and pulmonary afferents and is further modulated by central respiratory drive [ 28 – 32 ], the direct cardiac influence and the related decrease in intracardiac vagal control following PVI seem to be key in our patients.…”