Chronotropic incompetence and autonomic dysfunction as mechanisms of dyspnoea in patients with late stage cardiac amyloidosis

Nativi-Nicolau, José; Stehlik, Josef; Al-Dulaimi, Ragheed; Rodríguez, Carlos J.; Jaramillo, J. J.; Conte, Jorge; Kovacsovics, Tibor; Cowley, Jared; Abraham, Jo; Barrel, Kelsey; Drakos, Stavros G.; Ryan, John; Maurer, Mathew S.; Fang, James C.

doi:10.1080/13506129.2019.1582024

Cited by 4 publications

(3 citation statements)

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“…When correlating metaboreflex sensitivity with fESC, our results suggest that exaggerated metaboreflex sensitivity resulted in reduced stroke volume and cardiac output along with increased mean systemic arterial pressure and systemic vascular resistance, which have been related to chronic sympathetic over activation. A sympathovagal imbalance is further supported by previous studies showing chronotropic incompetence and blunted heart rate recovery in CA-TTR patients ( Nativi-Nicolau et al, 2019 ; Monfort et al, 2020 ; Nicol et al, 2021 ). Overall, abnormal electrochemical skin conductance and excessive metaboreflex activation in CA-TTR patients may be representative of an enhanced overall reactivity to cardiovascular sympatho-excitatory stimulus rather than a specific change in metaboreflex regulation within the skeletal muscle.…”

Section: Discussionsupporting

confidence: 68%

“…We conducted a pilot and exploratory study along with the purpose of testing the hypothesis of interest. Sample size calculation was based on heart failure differences and exercise pressor reflex studies ( Barrett-O'Keefe et al, 2018 ; Crisafulli, 2017 ; Guralnik et al, 1994 ; Nativi-Nicolau et al, 2019 ). Assuming alpha = 0.05 and power = 85%, a minimal sample size of 20 subjects was planned in order to highlight differences between groups and conditions.…”

Section: Methodsmentioning

confidence: 99%

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The ventilatory component of the muscle metaboreflex is overstimulated in transthyretin cardiac amyloidosis patients with poor aerobic capacity

et al. 2023

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Background: The exercise pressor reflex, i.e., metabo- and mechano-reflex, partially regulates the control of ventilation and cardiovascular function during exercise. Abnormal exercise pressor reflex response has been associated with exaggerated ventilatory drive, sympathovagal imbalance and exercise limitation in chronic heart failure patients. Whether metaboreflex is over-activated and participate to poor aerobic capacity in patients with hereditary transthyretin cardiac amyloidosis (CA-TTR) is unknown.Methods: Twenty-two CA-TTR patients (aged 76 ± 7, 68% male) with the V122I (p.Val142Ile) transthyretin underwent a thorough evaluation including heart rate variability metrics, electrochemical skin conductance (ESC), physical function cardiopulmonary exercise testing, and muscle metaboreflex assessment. Eleven control subjects were chosen for muscle metaboreflex assessment.Results: Age-matched controls (n = 11) and CA-TTR patients (n = 22) had similar metaboreflex sensitivity for heart rate, stroke volume, cardiac index and mean systemic arterial pressure. Compared with age-matched controls, metaboreflex sensitivity for systemic vascular resistance (−18.64% ± 6.91% vs 3.14% ± 23.35%) and minute-ventilation responses (−9.65% ± 14.83% vs 11.84% ± 23.1%) was markedly increased in CA-TTR patients. Values of ESC displayed positive correlations with stroke volume (r = 0.53, p = 0.011) and cardiac index (r = 0.51, p = 0.015) components of metaboreflex sensitivity, an inverse correlation with systemic vascular resistance (r = −0.55, p = 0.008) and a trend with mean arterial (r = −0.42, p = 0.052) components of metaboreflex sensitivity. Peak aerobic capacity (peak VO2%) displayed an inverse correlation with the ventilation component of metaboreflex sensitivity (r = −0.62, p = 0.015).Conclusion: Consistent with the “muscle hypothesis” in heart failure, it is proposed that deterioration of skeletal muscle function in hereditary CA-TTR patients may activate muscle metaboreflex, leading to an increase in ventilation and sensation of breathlessness, the perception of fatigue, and overall sympathetic activation.

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Section: Discussionsupporting

confidence: 68%

Section: Methodsmentioning

confidence: 99%

The ventilatory component of the muscle metaboreflex is overstimulated in transthyretin cardiac amyloidosis patients with poor aerobic capacity

et al. 2023

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“…The ventilatory response to exercise in these patients is further characterized by hyperventilation with rapid shallow breathing, in the absence of ventilatory limitation as evidenced by a normal ventilatory reserve ( Table 1 ). A common additional feature of patients with CA is chronotropic incompetence, defined as insufficient cardio-acceleration (typically less than 80–85%) at peak exercise ( 4 , 24 ). While the increase in normal stroke volume during exercise is lost in most patients with CA, cardiac output rises are primarily dependent on heart rate elevation.…”

Section: Characteristics Of Cardiopulmonary Exercise Testing In Cardi...mentioning

confidence: 99%

Diagnostic and Prognostic Values of Cardiopulmonary Exercise Testing in Cardiac Amyloidosis

Banydeen

Monfort

Inamo

et al. 2022

Front. Cardiovasc. Med.

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Cardiac amyloidosis (CA) is a myocardial disease characterized by extracellular amyloid infiltration throughout the heart, resulting in increased myocardial stiffness, and restrictive heart wall chamber behavior. Its diagnosis among patients hospitalized for cardiovascular diseases is becoming increasingly frequent, suggesting improved disease awareness, and higher diagnostic capacities. One predominant functional manifestation of patients with CA is exercise intolerance, objectified by reduced peak oxygen uptake (VO2 peak), and assessed by metabolic cart during cardiopulmonary exercise testing (CPET). Hemodynamic adaptation to exercise in patients with CA is characterized by low myocardial contractile reserve and impaired myocardial efficiency. Rapid shallow breathing and hyperventilation, in the absence of ventilatory limitation, are also typically observed in response to exercise. Ventilatory inefficiency is further suggested by an increased VE-VCO2 slope, which has been attributed to excessive sympathoexcitation and a high physiological dead space (VD/VT) ratio during exercise. Growing evidence now suggests that, in addition to well-established biomarker risk models, a reduced VO2 peak is potentially a strong and independent predictive factor of adverse patient outcomes, both for monoclonal immunoglobulin light chain (AL) or transthyretin (ATTR) CA. Besides generating prognostic information, CPET can be used for the evaluation of the impact of therapeutic interventions in patients with CA.

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Restrictive cardiac phenotype as primary cause of impaired aerobic capacity in Afro-Caribbean patients with val122ile variant transthyretin amyloid cardiomyopathy

Monfort

Banydeen

Demonière

et al. 2020

Amyloid

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Chronotropic incompetence and autonomic dysfunction as mechanisms of dyspnoea in patients with late stage cardiac amyloidosis

Cited by 4 publications

References 0 publications

The ventilatory component of the muscle metaboreflex is overstimulated in transthyretin cardiac amyloidosis patients with poor aerobic capacity

The ventilatory component of the muscle metaboreflex is overstimulated in transthyretin cardiac amyloidosis patients with poor aerobic capacity

Diagnostic and Prognostic Values of Cardiopulmonary Exercise Testing in Cardiac Amyloidosis

Restrictive cardiac phenotype as primary cause of impaired aerobic capacity in Afro-Caribbean patients with val122ile variant transthyretin amyloid cardiomyopathy

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